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Simovic A, Radomirovic M, Gligorijevic N, Milcic M, Bicanin M, Minic S, Stojanovic M, Stanic-Vucinic D, Cirkovic Velickovic T. Food-derived bioactive pigment phycocyanobilin binds to SARS-CoV-2 spike protein both covalently and noncovalently affecting its conformation and functionality. Arch Biochem Biophys 2025; 770:110475. [PMID: 40404003 DOI: 10.1016/j.abb.2025.110475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 05/16/2025] [Accepted: 05/19/2025] [Indexed: 05/24/2025]
Abstract
Phycocyanobilin (PCB), tetrapyrrole chromophore of Spirulina phycocyanin, is bilirubin analog and weak thiol-modifying agent. SARS-CoV-2 spike protein (SP) has bilirubin binding pocket, lacks free sulfhydryl, but it has two pairs of functionally important semi-stable disulfides reactive towards thiol-modifying agents. We investigated covalent and noncovalent binding of PCB to SP and its receptor-binding domain (RBD) and impact of covalent PCB conjugation to RBD on structure and binding to human angiotensin-converting enzyme 2 (ACE-2). PCB shows high-affinity for SP (Ka = 2.1 × 107 M-1), moderate-affinity for RBD (Ka = 8.4 × 104 M-1) and binds covalently to SP and RBD in reaction involving thiols. PCB binding alters RBD conformation. Molecular docking identified two binding sites of PCB to SP, bilirubin/biliverdin binding site and hydrophobic pocket of RBD in vicinity of Cys432, preferential target for covalent binding in in silico covalent docking of PCB to RBD. Redox proteomics mapped reactive Cys432, Cys391 and Cys525 in RBD. PCB-modified RBD exhibited reduced ability to bind to ACE-2. This is the first study demonstrating PCB reactivity towards semi-stable disulfides of proteins lacking free sulfhydryl groups. PCB may affect functionality and structure of SP and its RBD by noncovalent and covalent binding.
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Affiliation(s)
- Ana Simovic
- Centre of Excellence for Molecular Food Sciences and Department of Biochemistry, University of Belgrade, Faculty of Chemistry, 11000, Belgrade, Serbia
| | - Mirjana Radomirovic
- Centre of Excellence for Molecular Food Sciences and Department of Biochemistry, University of Belgrade, Faculty of Chemistry, 11000, Belgrade, Serbia
| | - Nikola Gligorijevic
- Center for Chemistry, University of Belgrade, Institute of Chemistry, Technology and Metallurgy, National Institute of the Republic of Serbia, 11000, Belgrade, Serbia
| | - Milos Milcic
- Centre of Excellence for Molecular Food Sciences and Department of Biochemistry, University of Belgrade, Faculty of Chemistry, 11000, Belgrade, Serbia
| | - Masa Bicanin
- Centre of Excellence for Molecular Food Sciences and Department of Biochemistry, University of Belgrade, Faculty of Chemistry, 11000, Belgrade, Serbia
| | - Simeon Minic
- Centre of Excellence for Molecular Food Sciences and Department of Biochemistry, University of Belgrade, Faculty of Chemistry, 11000, Belgrade, Serbia
| | - Marijana Stojanovic
- Department of Molecular Biology, Institute for Biological Research "Siniša Stanković", National Institute of the Republic of Serbia, University of Belgrade, 11000, Belgrade, Serbia
| | - Dragana Stanic-Vucinic
- Centre of Excellence for Molecular Food Sciences and Department of Biochemistry, University of Belgrade, Faculty of Chemistry, 11000, Belgrade, Serbia
| | - Tanja Cirkovic Velickovic
- Centre of Excellence for Molecular Food Sciences and Department of Biochemistry, University of Belgrade, Faculty of Chemistry, 11000, Belgrade, Serbia; Serbian Academy of Sciences and Arts, 11000, Belgrade, Serbia.
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Raspado O, Brack M, Brack O, Vivancos M, Esparcieux A, Cart-Tanneur E, Aouifi A. Oxidative Stress Markers and Prediction of Severity With a Machine Learning Approach in Hospitalized Patients With COVID-19 and Severe Lung Disease: Observational, Retrospective, Single-Center Feasibility Study. JMIR Form Res 2025; 9:e66509. [PMID: 40215478 PMCID: PMC12007842 DOI: 10.2196/66509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 02/19/2025] [Accepted: 02/20/2025] [Indexed: 04/17/2025] Open
Abstract
Background Serious pulmonary pathologies of infectious, viral, or bacterial origin are accompanied by inflammation and an increase in oxidative stress (OS). In these situations, biological measurements of OS are technically difficult to obtain, and their results are difficult to interpret. OS assays that do not require complex preanalytical methods, as well as machine learning methods for improving interpretation of the results, would be very useful tools for medical and care teams. Objective We aimed to identify relevant OS biomarkers associated with the severity of hospitalized patients' condition and identify possible correlations between OS biomarkers and the clinical status of hospitalized patients with COVID-19 and severe lung disease at the time of hospital admission. Methods All adult patients hospitalized with COVID-19 at the Infirmerie Protestante (Lyon, France) from February 9, 2022, to May 18, 2022, were included, regardless of the care service they used, during the respiratory infectious COVID-19 epidemic. We collected serous biomarkers from the patients (zinc [Zn], copper [Cu], Cu/Zn ratio, selenium, uric acid, high-sensitivity C-reactive protein [hs-CRP], oxidized low-density lipoprotein, glutathione peroxidase, glutathione reductase, and thiols), as well as demographic variables and comorbidities. A support vector machine (SVM) model was used to predict the severity of the patients' condition based on the collected data as a training set. Results A total of 28 patients were included: 8 were asymptomatic at admission (grade 0), 14 had mild to moderate symptoms (grade 1) and 6 had severe to critical symptoms (grade 3). As the first outcome, we found that 3 biomarkers of OS were associated with severity (Zn, Cu/Zn ratio, and thiols), especially between grades 0 and 1 and between grades 0 and 2. As a second outcome, we found that the SVM model could predict the level of severity based on a biological analysis of the level of OS, with only 7% misclassification on the training dataset. As an illustrative example, we simulated 3 different biological profiles (named A, B, and C) and submitted them to the SVM model. Profile B had significantly high Zn, low hs-CRP, a low Cu/Zn ratio, and high thiols, corresponding to grade 0. Profile C had low Zn, low selenium, high oxidized low-density lipoprotein, high glutathione peroxidase, a low Cu/Zn ratio, and low glutathione reductase, corresponding to grade 2. Conclusions The level of severity of pulmonary damage in patients hospitalized with COVID-19 was predicted using an SVM model; moderate to severe symptoms in patients were associated with low Zn, low plasma thiol, increased hs-CRP, and an increased Cu/Zn ratio among a panel of 10 biomarkers of OS. Since this panel does not require a complex preanalytical method, it can be used and studied in other pathologies associated with OS, such as infectious pathologies or chronic diseases.
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Affiliation(s)
- Olivier Raspado
- Infirmerie Protestante, 1 Chemin du Penthod, Caluire-et-Cuire, 69300, France, 33 0624576962
| | - Michel Brack
- Oxidative Stress College, La Garenne-Colombes, France
| | - Olivier Brack
- Statistique Industrielle Khi² Consulting (KSIC), Bayet, France
| | - Mélanie Vivancos
- Clinical Research and Innovation Department, Infirmerie Protestante, Caluire-et-Cuire, France
| | - Aurélie Esparcieux
- Infirmerie Protestante, 1 Chemin du Penthod, Caluire-et-Cuire, 69300, France, 33 0624576962
| | | | - Abdellah Aouifi
- Infirmerie Protestante, 1 Chemin du Penthod, Caluire-et-Cuire, 69300, France, 33 0624576962
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3
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Ghasemitarei M, Taeb H, Ghorbi T, Yusupov M, Ala-Nissila T, Bogaerts A. The effect of cysteine oxidation on conformational changes of SARS-CoV-2 spike protein using atomistic simulations. Sci Rep 2025; 15:6890. [PMID: 40011543 PMCID: PMC11865280 DOI: 10.1038/s41598-025-90918-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 02/17/2025] [Indexed: 02/28/2025] Open
Abstract
The SARS-CoV-2 Spike (S) protein plays a central role in viral entry into host cells, making it a key target for therapeutic interventions. Oxidative stress, often triggered during viral infections, can cause oxidation of cysteine in this protein. Here we investigate the impact of cysteine oxidation, specifically the formation of cysteic acid, on the conformational dynamics of the SARS-CoV-2 S protein using atomistic simulations. In particular, we examine how cysteine oxidation influences the transitions of the S protein's receptor-binding domain (RBD) between "down" (inaccessible) and "up" (accessible) states, which are critical for host cell receptor engagement. Using solvent-accessible surface area (SASA) analysis, we identify key cysteine residues susceptible to oxidation. The results of targeted molecular dynamics (TMD) and umbrella sampling (US) simulations reveal that oxidation reduces the energy barrier for RBD transitions by approximately 30 kJ mol-1, facilitating conformational changes and potentially enhancing viral infectivity. Furthermore, we analyze the interactions between oxidized cysteine residues and glycans, as well as alterations in hydrogen bonds and salt bridges. Our results show that oxidation disrupts normal RBD dynamics, influencing the energy landscape of conformational transitions. Our work provides novel insights into the role of cysteine oxidation in modulating the structural dynamics of the SARS-CoV-2 S protein, highlighting potential targets for antiviral strategies aimed at reducing oxidative stress or modifying post-translational changes. These findings contribute to a deeper understanding of viral infectivity and pathogenesis under oxidative conditions.
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Affiliation(s)
- Maryam Ghasemitarei
- Department of Applied Physics, Aalto University, P.O. Box 15600, 00076, Aalto, Espoo, Finland.
| | - Hoda Taeb
- Department of Physics, Simon Fraser University, Burnaby, Canada
| | - Tayebeh Ghorbi
- Laboratory of Experimental Biophysics, Centre for Advanced Technologies, 100174, Tashkent, Uzbekistan
| | - Maksudbek Yusupov
- Institute of Fundamental and Applied Research, National Research University TIIAME, 100000, Tashkent, Uzbekistan
- Department of Information Technologies, Tashkent International University of Education, 100207, Tashkent, Uzbekistan
| | - Tapio Ala-Nissila
- Department of Applied Physics, Aalto University, P.O. Box 15600, 00076, Aalto, Espoo, Finland
- Interdisciplinary Centre for Mathematical Modelling and Department of Mathematical Sciences, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK
| | - Annemie Bogaerts
- Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610, Antwerp, Belgium
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Wang S, Sun J, Hu Y, Zhang W, Qin B, Li M, Zhang N, Wang S, Zhou T, Liu M, Ma C, Deng X, Bai Y, Qu G, Liu L, Shi H, Zhou B, Li K, Yang B, Li S, Wang F, Ma J, Zhang L, Wang Y, An L, Liu W, Chang Q, Zhang R, Yin X, Yang Y, Ao Q, Ma Q, Yan S, Huang H, Song P, Zhao S, Gao L, Lu W, Xu L, Lei L, Wang K, Song Q, Zhang Z, Fang X, He Y, Zhang Q, Jia J, Zhu P. Clinical and Multiorgan Proteomics Characteristics of the Diverse Fatal Phase in Super Elderly Patients With SARS-CoV-2 Infection: A Descriptive Study. J Med Virol 2025; 97:e70207. [PMID: 39921383 DOI: 10.1002/jmv.70207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 01/14/2025] [Accepted: 01/25/2025] [Indexed: 02/10/2025]
Abstract
This study aims to identify the risk factors associated with clinical outcomes and the proteomic changes in organs related to fatal SARS-CoV-2 infection within the super-elderly population. This retrospective analysis included all elderly individuals with COVID-19 admitted to the Second Medical Center of PLA General Hospital from December 2022 to January 2023. The follow-up period ended on March 30, 2023. During this time, epidemiological, demographic, laboratory, and outcome data were analyzed descriptively. Proteomic sequencing was performed on super-elderly patients who died from COVID-19 at different stages of the disease. A total of 352 elderly COVID-19 patients, with a mean age of 89.84 ± 8.54 years, were included in this study. During a median follow-up period of 98 days, 79 patients died. Deceased patients were older and more likely to have cardiovascular and cerebrovascular diseases, with a lower prevalence of lipid-lowering therapy. The number of deaths in the acute and post-acute phases were 34 and 45, respectively. Proteomics data suggest that the immune systems of patients who died in the acute phase underwent a more rapid and severe onslaught. Patients in the post-acute phase showed higher levels of viral genome replication and a more robust immune response. However, the over-activation of the immune system led to systemic organ dysfunction. Effective management of comorbidities may improve the prognosis of COVID-19 in super-elderly patients. The continuous replication of the SARS-CoV-2 virus and its subsequent impact on the immune system are critical determinants of survival time in this demographic.
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Affiliation(s)
- Shuxia Wang
- Department of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Jin Sun
- Department of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Yazhuo Hu
- Institute of Geriatrics, The Second Medical Center, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, Chinese PLA General Hospital, Beijing, China
| | - Wei Zhang
- Department of Integrative Therapy, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Bangguo Qin
- Medical School of Chinese PLA, Beijing, China
| | - Man Li
- Department of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Nan Zhang
- Department of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Shengshu Wang
- Institute of Geriatrics, The Second Medical Center, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, Chinese PLA General Hospital, Beijing, China
| | - Tingyu Zhou
- National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Miao Liu
- Department of Anti-NBC Medicine, Graduate School of Chinese PLA General Hospital, Beijing, China
| | - Cong Ma
- Department of Health Medicine, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xinli Deng
- Department of Clinical Laboratory, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yongyi Bai
- Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Geping Qu
- Department of Respiratory and Critical Care Medicine, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lin Liu
- Department of Respiratory and Critical Care Medicine, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Hui Shi
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Bo Zhou
- Department of Neurology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Ke Li
- Department of Neurology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Bo Yang
- Department of Hematology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Suxia Li
- Department of Hematology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Fan Wang
- Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Jinling Ma
- Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Lu Zhang
- Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Yajuan Wang
- Department of Respiratory and Critical Care Medicine, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Li An
- Department of Respiratory and Critical Care Medicine, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Wenhui Liu
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Qing Chang
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Ru Zhang
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xi Yin
- Department of Neurology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yang Yang
- Department of Neurology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Qiangguo Ao
- Department of Nephrology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Qiang Ma
- Department of Nephrology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Shuangtong Yan
- Department of Endocrinology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Haili Huang
- Department of MedicaI Oncology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Peng Song
- Department of MedicaI Oncology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Shu Zhao
- Department of MedicaI Oncology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Linggen Gao
- Department of General Surgery, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Wenning Lu
- Department of General Surgery, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lining Xu
- Department of General Surgery, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Li Lei
- Department of Health Medicine, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Keyu Wang
- Department of Clinical Laboratory, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Qing Song
- Department of Critical Care Medicine, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zhijian Zhang
- Department of Respiratory and Critical Care Medicine, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xiangqun Fang
- Department of Respiratory and Critical Care Medicine, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yao He
- Institute of Geriatrics, The Second Medical Center, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, Chinese PLA General Hospital, Beijing, China
| | - Qi Zhang
- The Second Medical Center, PLA General Hospital, Beijing, China
| | - Jianjun Jia
- Institute of Geriatrics, The Second Medical Center, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, Chinese PLA General Hospital, Beijing, China
| | - Ping Zhu
- Department of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
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Razzaque MS, Wimalawansa SJ. Minerals and Human Health: From Deficiency to Toxicity. Nutrients 2025; 17:454. [PMID: 39940312 PMCID: PMC11820417 DOI: 10.3390/nu17030454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 01/24/2025] [Accepted: 01/24/2025] [Indexed: 02/14/2025] Open
Abstract
Minerals are essential nutrients that play critical roles in human health by regulating various physiological functions. Examples include bone development, enzyme function, nerve signaling, and the immune response. Both the deficiencies and toxicities of minerals can have significant health implications. Deficiencies in macrominerals such as calcium, magnesium, and phosphate can lead to osteoporosis (associated with falls and fractures), cardiovascular events, and neuromuscular dysfunction. Trace mineral deficiencies, such as iron and zinc. Selenium deficiency impairs oxygen transport, immune function, and antioxidant defenses, contributing to anemia, delaying wound healing, and increasing susceptibility to infectious diseases. Conversely, excessive intake of minerals can have severe health consequences. Hypercalcemia can cause kidney stones and cardiac arrhythmias as well as soft-tissue calcification, whereas excessive iron deposition can lead to oxidative stress and organ/tissue damage. Maintaining adequate mineral levels through a balanced diet, guided supplementation, and monitoring at-risk populations is essential for good health and preventing disorders related to deficiencies and toxicities. Public health interventions and education about dietary sources of minerals are critical for minimizing health risks and ensuring optimal well-being across populations. While a comprehensive analysis of all macro and micronutrients is beyond the scope of this article, we have chosen to focus on calcium, magnesium, and phosphate. We summarize the consequences of deficiency and the adverse events associated with the overconsumption of other minerals.
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Affiliation(s)
- Mohammed S. Razzaque
- Department of Medical Education, University of Texas, Rio Grande Valley, Edinburg, TX 78520, USA;
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Ahn G, Yoon HW, Jeong JH, Kim YH, Shin WR, Song MS, Ahn JY. Viral Mimetic Bacterial Outer Membrane Vesicles for Targeting Angiotensin-Converting Enzyme 2. Int J Nanomedicine 2025; 20:669-684. [PMID: 39835181 PMCID: PMC11745048 DOI: 10.2147/ijn.s497742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 01/01/2025] [Indexed: 01/22/2025] Open
Abstract
Purpose Outer membrane vesicles (OMVs) derived from Gram-negative bacteria naturally serve as a heterologous nano-engineering platform, functioning as effective multi-use nanovesicles for diagnostics, vaccines, and treatments against pathogens. To apply refined OMVs for human theranostic applications, we developed naturally exposed receptor-binding domain (RBD) OMVs grafted with antigen 43 as a minimal modular system targeting angiotensin-converting enzyme 2 (ACE2). Methods We constructed E. coli-derived OMVs using the antigen 43 autotransporter system to display RBD referred to as viral mimetic Ag43β700_RBD OMVs. Based on this, Ag43β700_RBD protein were expressed onto Escherichia coli (E. coli) membrane. Artificial viral mimetic Ag43β700_RBD OMVs were fabricated by self-assembly through membrane disruption of the Ag43β700_RBD E. coli using a chemical detergent mainly containing lysozyme. Through serial centrifugation to purify fabricated OMVs, spherical Ag43β700_RBD OMVs with an average diameter of 218 nm were obtained. The confirmation of the RBD expressed on OMVs was performed using trypsin treatment. Results Our viral mimetic Ag43β700_RBD OMVs had an impact on the theranostic studies: (i) angiotensin-converting enzyme 2 blockade assay, (ii) enzyme-linked immunosorbent assay for the OMVs, and (iii) intracellular uptake and neutralization assay. As serodiagnostic surrogates, Ag43β700_RBD OMVs were applied to ACE2 blockade and OMVs-ELISA assay to quantify neutralization antibodies (nAbs). They reduced the robust immune response in vitro, especially IL-6 and IL-1β. Experiments in mice, Ag43β700_RBD OMVs was successfully proven to be safe and effective; they produced a detectable level of nAbs with 39-58% neutralisation and reduced viral titres in the lungs and brain without weight loss. Conclusion The developed viral mimetic Ag43β700_RBD OMVs may therefore be applied as a nanovesicle-theranostic platform for further emerging infectious disease-related diagnosis, vaccination, and treatment.
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Affiliation(s)
- Gna Ahn
- Department of Microbiology, Chungbuk National University, Cheongju, Republic of Korea
- Center for Ecology and Environmental Toxicology, Chungbuk National University, Cheongju, Republic of Korea
| | - Hyo-Won Yoon
- Department of Microbiology, Chungbuk National University, Cheongju, Republic of Korea
| | - Ju Hwan Jeong
- Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Republic of Korea
| | - Yang-Hoon Kim
- Department of Microbiology, Chungbuk National University, Cheongju, Republic of Korea
| | - Woo-Ri Shin
- Department of Microbiology, Chungbuk National University, Cheongju, Republic of Korea
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA
- Department of Animal Bioscience & Integrated Biotechnology, Gyeongsang National University, Jinju, Republic of Korea
| | - Min-Suk Song
- Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea
| | - Ji-Young Ahn
- Department of Microbiology, Chungbuk National University, Cheongju, Republic of Korea
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Okada K, Kin C, Yamashita Y, Kawamura S, Sato K, Chiba K, Miyake H. Possible mechanisms of spermatogenic dysfunction induced by viral infections: Insights from COVID-19. Reprod Med Biol 2025; 24:e12625. [PMID: 39845480 PMCID: PMC11751869 DOI: 10.1002/rmb2.12625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 12/17/2024] [Indexed: 01/24/2025] Open
Abstract
Background As the COVID-19 pandemic nears resolution in 2024, the mechanisms by which SARS-CoV-2 and other viral infections induce spermatogenic dysfunction remain poorly understood. This review examines the mechanisms by which viral infections, particularly COVID-19, disrupt spermatogenesis and highlights the implications for male reproductive health. While reports suggest that spermatogenic dysfunction caused by COVID-19 is mild and transient, these findings may have broader applications in understanding and treating spermatogenic dysfunction caused by future viral infections. Methods The PubMed database was searched to identify original and review articles investigating the mechanisms by which viral infections, particularly SARS-CoV-2, contribute to spermatogenic dysfunction. Main Findings SARS-CoV-2 affects the testis through multiple mechanisms, including ACE2 receptor-mediated entry, direct viral damage, inflammatory response, blood-testis barrier disruption, hormonal imbalance, oxidative stress, and impaired spermatogenesis. The combination of these factors can disrupt testicular function and highlights the complexity of the effects of COVID-19 on male reproductive health. Conclusion COVID-19 may disrupt spermatogenesis through direct testicular infection, systemic inflammation, hormonal disruption, and oxidative stress. Ongoing research, vaccination efforts, and clinical vigilance are essential to address these challenges and develop effective treatment and prevention strategies.
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Affiliation(s)
- Keisuke Okada
- Department of UrologyKobe City Medical Center West HospitalKobeJapan
- Division of Urology, Department of Organs TherapeuticsKobe University Graduate School of MedicineKobeJapan
| | - Chanhyon Kin
- Division of Urology, Department of Organs TherapeuticsKobe University Graduate School of MedicineKobeJapan
| | - Yosuke Yamashita
- Division of Urology, Department of Organs TherapeuticsKobe University Graduate School of MedicineKobeJapan
| | - Shun Kawamura
- Division of Urology, Department of Organs TherapeuticsKobe University Graduate School of MedicineKobeJapan
| | - Katsuya Sato
- Division of Urology, Department of Organs TherapeuticsKobe University Graduate School of MedicineKobeJapan
| | - Koji Chiba
- Division of Urology, Department of Organs TherapeuticsKobe University Graduate School of MedicineKobeJapan
| | - Hideaki Miyake
- Division of Urology, Department of Organs TherapeuticsKobe University Graduate School of MedicineKobeJapan
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Amara A, Trabelsi S, Hai A, Zaidi SHH, Siddiqui F, Alsaeed S. Equivocating and Deliberating on the Probability of COVID-19 Infection Serving as a Risk Factor for Lung Cancer and Common Molecular Pathways Serving as a Link. Pathogens 2024; 13:1070. [PMID: 39770330 PMCID: PMC11728627 DOI: 10.3390/pathogens13121070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 11/27/2024] [Accepted: 12/04/2024] [Indexed: 01/30/2025] Open
Abstract
The COVID-19 infection caused by SARS-CoV-2 in late 2019 posed unprecedented global health challenges of massive proportions. The persistent effects of COVID-19 have become a subject of significant concern amongst the medical and scientific community. This article aims to explore the probability of a link between the COVID-19 infection and the risk of lung cancer development. First, this article reports that SARS-CoV-2 induces severe inflammatory response and cellular stress, potentially leading to tumorigenesis through common pathways between SARS-CoV-2 infection and cancer. These pathways include the JAK/STAT3 pathway which is activated after the initiation of cytokine storm following SARS-CoV-2 infection. This pathway is involved in cellular proliferation, differentiation, and immune homeostasis. The JAK/STAT3 pathway is also hyperactivated in lung cancer which serves as a link thereof. It predisposes patients to lung cancer through myriad molecular mechanisms such as DNA damage, genomic instability, and cell cycle dysregulation. Another probable pathway to tumorigenesis is based on the possibility of an oncogenic nature of SARS-CoV-2 through hijacking the p53 protein, leading to cell oxidative stress and interfering with the DNA repair mechanisms. Finally, this article highlights the overexpression of the SLC22A18 gene in lung cancer. This gene can be overexpressed by the ZEB1 transcription factor, which was found to be highly expressed during COVID-19 infection.
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Affiliation(s)
- Abdelbasset Amara
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia; (A.H.); (F.S.); (S.A.)
- Center for Health Research, Northern Border University, Arar 91431, Saudi Arabia;
| | - Saoussen Trabelsi
- Center for Health Research, Northern Border University, Arar 91431, Saudi Arabia;
- Department of Community Health, Faculty of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia
| | - Abdul Hai
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia; (A.H.); (F.S.); (S.A.)
| | - Syeda Huma H. Zaidi
- Department of Chemistry, Faculty of Science, Northern Border University, Arar 91431, Saudi Arabia;
| | - Farah Siddiqui
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia; (A.H.); (F.S.); (S.A.)
| | - Sami Alsaeed
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia; (A.H.); (F.S.); (S.A.)
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9
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C L B Ferreira B, Hannard M, Lozano-Garcia M, Aston L, Tejeda G, Domena JB, Bernard B, Chen J, Bartoli M, Rech Tondin A, Zhou Y, Scorzari A, Perrone CS, Tagliaferro A, Deo S, Daunert S, Dumont CM, Leblanc RM. Investigating the Significances of Thiol Functionalities in SARS-CoV-2 Using Carbon Dots for Viral Inhibition. ACS APPLIED MATERIALS & INTERFACES 2024; 16:58439-58451. [PMID: 39422222 DOI: 10.1021/acsami.4c14482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
While the World Health Organization has declared the end of the SARS-CoV-2 public health emergency, studies related to corona viruses are still under course. As of 2024, the severity of COVID-19 has diminished with current treatments and vaccinations. However, individuals can still face severe complications, highlighting the importance of ongoing research into innovative treatments for current and future coronavirus-related diseases. This study approaches the mechanism of viral entrance into the host cells and the current evidence on the use of sulfhydryl groups for the COVID-19 treatment. Certain thiol drugs, a key contributor to inflammatory processes, exhibit both viral inhibition properties and the potential to regulate cellular oxidative stress by scavenging free radicals. Herein, we developed biocompatible thiol-functionalized carbon dots (CDs) and investigated the correlation between the number of thiols and pseudo-SARS-CoV-2 inhibition, reactive oxygen species (ROS) scavenging, and anti-inflammatory response. The free-radical scavenging experiment and the ROS cellular assay indicate that thiolated CDs serve as effective reducing agents and potential regulators of cellular oxidative stress. The CDs also demonstrated good cell viability alongside significant antiviral capabilities, with inhibition levels up to 60.4%. Furthermore, the flow cytometry results suggest that in an inflammatory environment, the presence of thiolated CDs promotes an anti-inflammatory response. Overall, the results demonstrate a strong correlation between the number of thiols and the increased efficacy observed across experiments, presenting thiolated CDs as promising candidates to prevent and treat COVID-19 infection.
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Affiliation(s)
- Braulio C L B Ferreira
- Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States
| | - Maxence Hannard
- Empa - Swiss Federal Laboratories for Materials Science and Technology, Dübendorf 8600, Switzerland
| | - Mercedes Lozano-Garcia
- Department of Biochemistry & Molecular Biology, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States
| | - Lillian Aston
- Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States
| | - Giancarlo Tejeda
- Department of Biomedical Engineering, University of Miami, 1251 Memorial Drive, Coral Gables, Florida 33146, United States
| | - Justin B Domena
- Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States
| | - Brianna Bernard
- Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States
| | - Jiuyan Chen
- Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States
| | - Mattia Bartoli
- Center for Sustainable Future Technologies, Italian Institute of Technology, Via Livorno 60, Turin 10144, Italy
| | - Arthur Rech Tondin
- Department of Biochemistry & Molecular Biology, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States
| | - Yiqun Zhou
- Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States
| | - Annalise Scorzari
- Department of Chemistry, Clemson University, Clemson, South Carolina 29634, United States
| | - Caitlyn S Perrone
- Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States
| | - Alberto Tagliaferro
- Department of Applied Science and Technology, Politecnico di Torino, Torino 10129 Italy
| | - Sapna Deo
- Department of Biochemistry & Molecular Biology, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States
| | - Sylvia Daunert
- Department of Biochemistry & Molecular Biology, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States
| | - Courtney M Dumont
- Department of Biomedical Engineering, University of Miami, 1251 Memorial Drive, Coral Gables, Florida 33146, United States
| | - Roger M Leblanc
- Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States
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10
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Avdonin PP, Blinova MS, Serkova AA, Komleva LA, Avdonin PV. Immunity and Coagulation in COVID-19. Int J Mol Sci 2024; 25:11267. [PMID: 39457048 PMCID: PMC11508857 DOI: 10.3390/ijms252011267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/23/2024] [Accepted: 10/15/2024] [Indexed: 10/28/2024] Open
Abstract
Discovered in late 2019, the SARS-CoV-2 coronavirus has caused the largest pandemic of the 21st century, claiming more than seven million lives. In most cases, the COVID-19 disease caused by the SARS-CoV-2 virus is relatively mild and affects only the upper respiratory tract; it most often manifests itself with fever, chills, cough, and sore throat, but also has less-common mild symptoms. In most cases, patients do not require hospitalization, and fully recover. However, in some cases, infection with the SARS-CoV-2 virus leads to the development of a severe form of COVID-19, which is characterized by the development of life-threatening complications affecting not only the lungs, but also other organs and systems. In particular, various forms of thrombotic complications are common among patients with a severe form of COVID-19. The mechanisms for the development of thrombotic complications in COVID-19 remain unclear. Accumulated data indicate that the pathogenesis of severe COVID-19 is based on disruptions in the functioning of various innate immune systems. The key role in the primary response to a viral infection is assigned to two systems. These are the pattern recognition receptors, primarily members of the toll-like receptor (TLR) family, and the complement system. Both systems are the first to engage in the fight against the virus and launch a whole range of mechanisms aimed at its rapid elimination. Normally, their joint activity leads to the destruction of the pathogen and recovery. However, disruptions in the functioning of these innate immune systems in COVID-19 can cause the development of an excessive inflammatory response that is dangerous for the body. In turn, excessive inflammation entails activation of and damage to the vascular endothelium, as well as the development of the hypercoagulable state observed in patients seriously ill with COVID-19. Activation of the endothelium and hypercoagulation lead to the development of thrombosis and, as a result, damage to organs and tissues. Immune-mediated thrombotic complications are termed "immunothrombosis". In this review, we discuss in detail the features of immunothrombosis associated with SARS-CoV-2 infection and its potential underlying mechanisms.
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Affiliation(s)
| | | | | | | | - Pavel V. Avdonin
- Koltzov Institute of Developmental Biology RAS, ul. Vavilova, 26, 119334 Moscow, Russia; (P.P.A.)
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11
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Okeke KI, Ahamefule CS, Nnabuife OO, Orabueze IN, Iroegbu CU, Egbe KA, Ike AC. Antiseptics: An expeditious third force in the prevention and management of coronavirus diseases. CURRENT RESEARCH IN MICROBIAL SCIENCES 2024; 7:100293. [PMID: 39497935 PMCID: PMC11532748 DOI: 10.1016/j.crmicr.2024.100293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2024] Open
Abstract
Notably, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19) have all had significant negative impact on global health and economy. COVID-19 alone, has resulted to millions of deaths with new cases and mortality still being reported in its various waves. The development and use of vaccines have not stopped the transmission of SARS coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, even among vaccinated individuals. The use of vaccines and curative drugs should be supplemented with adoption of simple hygiene preventive measures in the fight against the spread of the virus, especially for healthcare workers. Several virucidal topical antiseptics, such as povidone-iodine (PVP-I), citrox, cyclodextrins among others, have been demonstrated to be efficacious in the inactivation of SARS-CoV-2 and other coronaviruses in both in vitro and in vivo studies. The strategic application of these virucidal formulations could provide the additional impetus needed to effectively control the spread of the virus. We have here presented a simple dimension towards curtailing the dissemination of COVID-19, and other coronaviruses, through the application of effective oral, nasal and eye antiseptics among patients and medical personnel. We have further discussed the mechanism of action of some of these commonly available virucidal solutions while also highlighting some essential controversies in their use.
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Affiliation(s)
- Kizito I. Okeke
- Department of Microbiology, Faculty of Biological Sciences, University of Nigeria, Nsukka 410001 Enugu State, Nigeria
| | - Chukwuemeka Samson Ahamefule
- Department of Microbiology, Faculty of Biological Sciences, University of Nigeria, Nsukka 410001 Enugu State, Nigeria
| | - Obianuju O. Nnabuife
- Department of Microbiology, Faculty of Biological Sciences, University of Nigeria, Nsukka 410001 Enugu State, Nigeria
| | - Ibuchukwu N. Orabueze
- Department of Medical Microbiology, University of Nigeria Teaching Hospital Enugu, Enugu State, Nigeria
| | - Christian U. Iroegbu
- Department of Microbiology, Cross River University of Technology, Calabar, Cross River State, Nigeria
| | - Kingsley A. Egbe
- Department of Microbiology, Faculty of Biological Sciences, University of Nigeria, Nsukka 410001 Enugu State, Nigeria
| | - Anthony C. Ike
- Department of Microbiology, Faculty of Biological Sciences, University of Nigeria, Nsukka 410001 Enugu State, Nigeria
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12
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Özgöçer T, Çelik H, Ceylan MR. Dynamic Thiol-Disulfide Homeostasis Post-COVID-19 Depends on Age, Gender, and Symptom Severity. Cureus 2024; 16:e72097. [PMID: 39575049 PMCID: PMC11581460 DOI: 10.7759/cureus.72097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/22/2024] [Indexed: 11/24/2024] Open
Abstract
INTRODUCTION It has been indicated that the thiol-disulfide homeostasis plays a role in the pathogenesis of COVID-19 infection. We assessed the impact on the thiol-disulfide homeostasis at 15-day intervals until 60 days, implicated in the pathogenesis of COVID-19, and its clinical relevance in disease progression. METHODS In this study, 43 COVID-19 patients (18 females and 25 males) were categorized based on symptom severity, age group, and body mass index. Serum samples were collected on days 15, 30, 45, and 60 after COVID-19 diagnosis. Thiol and disulfide parameters were measured in the collected serum samples using spectrophotometric methods. RESULTS Serum thiol levels were higher in females and disulfide levels in males (p<0.05). Disulfide levels increased in those older on 15-day post-symptom onset (p<0.05). Serum native thiol levels were higher in patients with moderate and severe symptom severity (p<0.05) than in those with mild severity. The symptoms of chest pain, shortness of breath, loss of taste, and loss of appetite were negatively correlated with thiol levels (p<0.05). CONCLUSIONS This study suggested critical findings of higher disulfide levels in older age and men, even in the weeks after disease onset. This discovery is significant as it could pave the way for interventions to repair thiol-disulfide homeostasis, potentially transforming the treatment of this group. Moreover, native thiols can point to disease severity even weeks after the onset of symptoms.
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Affiliation(s)
| | - Hakim Çelik
- Physiology, Harran University, Şanlıurfa, TUR
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13
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Beretti F, Gatti M, Ricchi F, Lipani F, Cortelli P, Cermelli C, Maraldi T. Neurotoxic effects of coronavirus: Potential implications in Alzheimer's onset and progression. Exp Neurol 2024; 380:114908. [PMID: 39089439 DOI: 10.1016/j.expneurol.2024.114908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 07/04/2024] [Accepted: 07/29/2024] [Indexed: 08/04/2024]
Abstract
The COVID-19, caused by SARS-CoV-2, first affects the respiratory tract but evidence is emerging that the virus, reaching the central nervous system (CNS), can lead to severe neurological disorders. In particular, CoV infection could cause an acceleration of the neurodegenerative process. On the other hand, patients diagnosed with Alzheimer's disease (AD) develop more serious forms of COVID-19 with worse relapses. Therefore, understanding the connection between the two pathologies, AD and infection by coronavirus, could help in the development of new therapeutic approaches to counter them. We used the SH-SY5Y cell line differentiated into neurons, as widely used in studies of AD if supplemented with exogenous fibrillary β-amyloid (Aβ). As a glial counterpart, human microglia (HMC3) and astrocytic (D54MG) cell lines were used to create co-cultures with neurons via transwell systems. In these experimental models, we generated infection with the Human Coronavirus OC43 (HCoV-OC43), a low-risk model of SARS-CoV-2. Our results suggest that the infection by HCoV-OC43 leads to a neurotoxic effect not depending on an already present event of Aβ deposition. Indeed, unlike microglia, neurons and even more astrocytes are susceptible to CoV infection and, although the infection does not show a cytotoxic effect in the neurons in the first few days, significant alterations at a biochemical and morphological level have been observed, suggesting that the neurons are reacting to a stressful condition, including the prodromal and neurodegenerative features of AD. Interestingly, the interaction of infected astrocytes with the neurons resulted in the manifestation of signs of neurodegeneration, such as amyloid-beta deposition. By using exogenous fibrillary Aβ, as an AD in vitro model, our data suggest that there is an aggravating effect both on the infection itself and on the neurological disease progression. In conclusion, the results of this study suggest a causal interplay between HCoV-OC43 and neurological diseases and demonstrate that the co-presence of different CNS cell populations is the necessary condition to study the pathogenic effects in vitro as a whole.
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Affiliation(s)
- Francesca Beretti
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy
| | - Martina Gatti
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy
| | - Francesco Ricchi
- Department of Surgery Medicine Dentistry and Morphological Sciences with an Interest in Transplant Oncology, University of Modena and Reggio Emilia, Modena, Italy
| | - Francesco Lipani
- Department of Surgery Medicine Dentistry and Morphological Sciences with an Interest in Transplant Oncology, University of Modena and Reggio Emilia, Modena, Italy
| | - Pietro Cortelli
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Italy
| | - Claudio Cermelli
- Department of Surgery Medicine Dentistry and Morphological Sciences with an Interest in Transplant Oncology, University of Modena and Reggio Emilia, Modena, Italy
| | - Tullia Maraldi
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy.
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14
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Davis DA, Nair A, Astter Y, Treco E, Peyser B, Gussio R, Nguyen T, Eaton B, Postnikova E, Murphy M, Shrestha P, Bulut H, Hattorri SI, Mitsuya H, Yarchoan R. Discovery of a nasal spray steroid, tixocortol, as an inhibitor of SARS-CoV-2 main protease and viral replication. RSC Med Chem 2024; 15:d4md00454j. [PMID: 39371432 PMCID: PMC11450544 DOI: 10.1039/d4md00454j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 09/15/2024] [Indexed: 10/08/2024] Open
Abstract
Coronaviruses rely on the viral-encoded chymotrypsin-like main protease (Mpro or 3CLpro) for replication and assembly. Our previous research on Mpro of SARS-CoV-2 identified cysteine 300 (Cys300) as a potential allosteric site of Mpro inhibition. Here, we identified tixocortol (TX) as a covalent modifier of Cys300 which inhibits Mpro activity in vitro as well as in a cell-based Mpro expression assay. Most importantly TX inhibited SARS-CoV-2 replication in ACE2 expressing HeLa cells. Biochemical analysis and kinetic assays were consistent with TX acting as a non-competitive inhibitor. By contrast, TX was a weaker inhibitor and modifier of C300S Mpro, confirming a role for Cys300 in inhibition of WT Mpro but also providing evidence for an additional Cys target. TX pivalate (TP), a prodrug for TX that was previously marketed as a nasal spray, also inhibited SARS-CoV-2 replication in HeLa-ACE2 cells at low micromolar IC50s. These studies suggest that TX and/or TP could possibly be repurposed for the prevention and/or treatment of SARS-CoV-2 infection.
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Affiliation(s)
- David A Davis
- HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute Bethesda MD USA
| | - Ashwin Nair
- HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute Bethesda MD USA
| | - Yana Astter
- HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute Bethesda MD USA
| | - Emma Treco
- HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute Bethesda MD USA
| | - Brian Peyser
- Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health USA
| | - Rick Gussio
- Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory for Cancer Research Frederick MD 21702 USA
- Computational Institute for Health and Environmental Research, (CIFHER.ORG) Riverside 5, RM 4076, 8490 Progress Dr. Frederick MD 21701 USA
| | - Tam Nguyen
- Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health USA
| | - Brett Eaton
- Integrated Research Facility at Fort Detrick 8200 Research Plaza Frederick MD 21702 USA
| | - Elena Postnikova
- Integrated Research Facility at Fort Detrick 8200 Research Plaza Frederick MD 21702 USA
| | - Michael Murphy
- Integrated Research Facility at Fort Detrick 8200 Research Plaza Frederick MD 21702 USA
| | - Prabha Shrestha
- HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute Bethesda MD USA
| | - Haydar Bulut
- HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute Bethesda MD USA
| | - Shin-Ichiro Hattorri
- Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute 1-21-1 Toyama Shinjuku-ku Tokyo 162-8655 Japan
| | - Hiroaki Mitsuya
- HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute Bethesda MD USA
- Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute 1-21-1 Toyama Shinjuku-ku Tokyo 162-8655 Japan
| | - Robert Yarchoan
- HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute Bethesda MD USA
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15
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Saha P, Talwar P. Idiopathic pulmonary fibrosis (IPF): disease pathophysiology, targets, and potential therapeutic interventions. Mol Cell Biochem 2024; 479:2181-2194. [PMID: 37707699 DOI: 10.1007/s11010-023-04845-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 08/26/2023] [Indexed: 09/15/2023]
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive, degenerative pulmonary condition. Transforming growth factor (TGF)-β, platelet-derived growth factor (PDGF), and tumor necrosis factor-α (TNF-α) are the major modulators of IPF that mediate myofibroblast differentiation and promote fibrotic remodeling of the lung. Cigarette smoke, asbestos fiber, drugs, and radiation are known to favor fibrotic remodeling of the lungs. Oxidative stress in the endoplasmic reticulum (ER) also leads to protein misfolding and promotes ER stress, which is predominant in IPF. This phenomenon further results in excess reactive oxygen species (ROS) aggregation, increasing oxidative stress. During protein folding in the ER, thiol groups on the cysteine residue are oxidized and disulfide bonds are formed, which leads to the production of hydrogen peroxide (H2O2) as a by-product. With the accumulation of misfolded proteins in the ER, multiple signaling cascades are initiated by the cell, collectively termed as the unfolded protein response (UPR). UPR also induces ROS production within the ER and mitochondria and promotes both pro-apoptotic and pro-survival pathways. The prevalence of post-COVID-19 pulmonary fibrosis (PCPF) is 44.9%, along with an alarming increase in "Coronavirus Disease 2019" (COVID-19) comorbidities. Fibrotic airway remodeling and declined lung function are the common endpoints of SARS-CoV-2 infection and IPF. Flavonoids are available in our dietary supplements and exhibit medicinal properties. Apigenin is a flavonoid found in plants, including chamomile, thyme, parsley, garlic, guava, and broccoli, and regulates several cellular functions, such as oxidative stress, ER stress, and fibrotic responses. In this study, we focus on the IPF and COVID-19 pathogenesis and the potential role of Apigenin in addressing disease progression.
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Affiliation(s)
- Pritha Saha
- Apoptosis and Cell Survival Research Laboratory, 412G Pearl Research Park, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India
| | - Priti Talwar
- Apoptosis and Cell Survival Research Laboratory, 412G Pearl Research Park, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India.
- Apoptosis and Cell Survival Research Laboratory, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India.
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16
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Yang D. TRPA1-Related Diseases and Applications of Nanotherapy. Int J Mol Sci 2024; 25:9234. [PMID: 39273183 PMCID: PMC11395144 DOI: 10.3390/ijms25179234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 07/30/2024] [Accepted: 08/23/2024] [Indexed: 09/15/2024] Open
Abstract
Transient receptor potential (TRP) channels, first identified in Drosophila in 1969, are multifunctional ion channels expressed in various cell types. Structurally, TRP channels consist of six membrane segments and are classified into seven subfamilies. Transient receptor potential ankyrin 1 (TRPA1), the first member of the TRPA family, is a calcium ion affinity non-selective cation channel involved in sensory transduction and responds to odors, tastes, and chemicals. It also regulates temperature and responses to stimuli. Recent studies have linked TRPA1 to several disorders, including chronic pain, inflammatory diseases, allergies, and respiratory problems, owing to its activation by environmental toxins. Mutations in TRPA1 can affect the sensory nerves and microvasculature, potentially causing nerve pain and vascular problems. Understanding the function of TRPA1 is important for the development of treatments for these diseases. Recent developments in nanomedicines that target various ion channels, including TRPA1, have had a significant impact on disease treatment, providing innovative alternatives to traditional disease treatments by overcoming various adverse effects.
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Affiliation(s)
- Dongki Yang
- Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of Korea
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17
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Wang D, Shi Y, Cheng Z, Luo L, Cheng K, Gan S, Liu C, Chen Z, Yang B. A Toxoplasma gondii thioredoxin with cell adhesion and antioxidant function. Front Cell Infect Microbiol 2024; 14:1404120. [PMID: 39211799 PMCID: PMC11358088 DOI: 10.3389/fcimb.2024.1404120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024] Open
Abstract
Background Toxoplasma gondii (T. gondii) is a widespread, zoonotic protozoan intracellular parasite with a complex life cycle, which can cause toxoplasmosis, a potentially serious disease. During the invasion process, T. gondii proteins first bind to the relevant host cell receptors, such as glycosaminoglycan molecule (GAG-binding motif), which is one of the main receptors for parasites or virus to infect host cells. However, research on TGME49_216510 (T. gondii Trx21), a protein from Toxoplasma gondii, is limited. Methods Bioinformatics analysis of the Trx21 protein was performed firstly. And specific primers were then designed using the conserved domain and GAG-binding motif to amplify, express, and purify a fragment of the Trx21 protein. The purified Trx21-GST protein was used for antioxidant and cell adhesion experiments. Simultaneously, mice were immunized with Trx21-His to generate specific polyclonal antibodies for subcellular localization analysis. Results The Trx21 protein, consisting of 774 amino acids, included a transmembrane region, three GAG-binding motifs, and a Thioredoxin-like domain. The recombinant Trx21-His protein had a molecular mass of about 31 kDa, while the Trx21-GST protein had a molecular mass of about 55 kDa, which was analyzed by SDS-PAGE and Western blot. Subcellular localization analysis by IFA revealed that Trx21 is predominantly distributed in the cytoplasm of T. gondii. Furthermore, Trx21 exhibited a protective effect on supercoiled DNA against metal-catalyzed oxidation (MCO) and demonstrated adhesion abilities to Vero cells. Conclusions These results indicate that Trx21 plays an important role in host cell interaction and oxidative damage.
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Affiliation(s)
- Dawei Wang
- College of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University, Jinzhou, Liaoning, China
- Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Yuyi Shi
- College of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University, Jinzhou, Liaoning, China
- Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Ziwen Cheng
- Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, Liaoning, China
- College of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Like Luo
- Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, Liaoning, China
- College of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Kuo Cheng
- Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, Liaoning, China
- College of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Shengqi Gan
- College of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University, Jinzhou, Liaoning, China
- Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Che Liu
- College of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University, Jinzhou, Liaoning, China
- Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Zeliang Chen
- Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Baoling Yang
- Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, Liaoning, China
- College of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning, China
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18
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Tisch C, Xourgia E, Exadaktylos A, Ziaka M. Potential use of sodium glucose co-transporter 2 inhibitors during acute illness: a systematic review based on COVID-19. Endocrine 2024; 85:660-675. [PMID: 38448675 PMCID: PMC11291544 DOI: 10.1007/s12020-024-03758-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/19/2024] [Indexed: 03/08/2024]
Abstract
OBJECTIVE SGLT-2i are increasingly recognized for their benefits in patients with cardiometabolic risk factors. Additionally, emerging evidence suggests potential applications in acute illnesses, including COVID-19. This systematic review aims to evaluate the effects of SGLT-2i in patients facing acute illness, particularly focusing on SARS-CoV-2 infection. METHODS Following PRISMA guidelines, a systematic search of PubMed, Scopus, medRxiv, Research Square, and Google Scholar identified 22 studies meeting inclusion criteria, including randomized controlled trials and observational studies. Data extraction and quality assessment were conducted independently. RESULTS Out of the 22 studies included in the review, six reported reduced mortality in DM-2 patients taking SGLT-2i, while two found a decreased risk of hospitalization. Moreover, one study demonstrated a lower in-hospital mortality rate in DM-2 patients under combined therapy of metformin plus SGLT-2i. However, three studies showed a neutral effect on the risk of hospitalization. No increased risk of developing COVID-19 was associated with SGLT-2i use in DM-2 patients. Prior use of SGLT-2i was not associated with ICU admission and need for MV. The risk of acute kidney injury showed variability, with inconsistent evidence regarding diabetic ketoacidosis. CONCLUSION Our systematic review reveals mixed findings on the efficacy of SGLT-2i use in COVID-19 patients with cardiometabolic risk factors. While some studies suggest potential benefits in reducing mortality and hospitalizations, others report inconclusive results. Further research is needed to clarify optimal usage and mitigate associated risks, emphasizing caution in clinical interpretation.
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Affiliation(s)
- Carmen Tisch
- Department of Internal Medicine, Thun General Hospital, Thun, Switzerland
| | - Eleni Xourgia
- Department of Cardiology, Inselspital, University Hospital, University of Bern, 3008, Bern, Switzerland
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland
| | - Aristomenis Exadaktylos
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland
| | - Mairi Ziaka
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland.
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Hati S, Bhattacharyya S. Writing a literature review as a class project in an upper-level undergraduate biochemistry course. BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION : A BIMONTHLY PUBLICATION OF THE INTERNATIONAL UNION OF BIOCHEMISTRY AND MOLECULAR BIOLOGY 2024; 52:311-316. [PMID: 38193602 DOI: 10.1002/bmb.21814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 12/10/2023] [Accepted: 12/30/2023] [Indexed: 01/10/2024]
Abstract
A literature review is an important part of conducting academic research. Knowing how to conduct a literature search and write a high-quality literature review is a valuable skill. Herein, the authors describe the method of introducing a literature review writing exercise in an upper-level biochemistry course. Since 2020, authors have collaborated with numerous undergraduates writing literature reviews on topics in biochemistry that resulted in peer-reviewed publications. Authors believe that this unique idea of providing a course-based undergraduate research experience (CURE) to many undergraduates, especially those who otherwise do not receive collaborative research experience through traditional research paths, must be shared with other instructors.
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Affiliation(s)
- Sanchita Hati
- Department of Chemistry and Biochemistry, University of Wisconsin-Eau Claire, Eau Claire, Wisconsin, USA
| | - Sudeep Bhattacharyya
- Department of Chemistry and Biochemistry, University of Wisconsin-Eau Claire, Eau Claire, Wisconsin, USA
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20
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Rogozin IB, Saura A, Poliakov E, Bykova A, Roche-Lima A, Pavlov YI, Yurchenko V. Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2. Int J Mol Sci 2024; 25:3696. [PMID: 38612505 PMCID: PMC11011937 DOI: 10.3390/ijms25073696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 03/22/2024] [Accepted: 03/23/2024] [Indexed: 04/14/2024] Open
Abstract
SARS-CoV-2 has accumulated many mutations since its emergence in late 2019. Nucleotide substitutions leading to amino acid replacements constitute the primary material for natural selection. Insertions, deletions, and substitutions appear to be critical for coronavirus's macro- and microevolution. Understanding the molecular mechanisms of mutations in the mutational hotspots (positions, loci with recurrent mutations, and nucleotide context) is important for disentangling roles of mutagenesis and selection. In the SARS-CoV-2 genome, deletions and insertions are frequently associated with repetitive sequences, whereas C>U substitutions are often surrounded by nucleotides resembling the APOBEC mutable motifs. We describe various approaches to mutation spectra analyses, including the context features of RNAs that are likely to be involved in the generation of recurrent mutations. We also discuss the interplay between mutations and natural selection as a complex evolutionary trend. The substantial variability and complexity of pipelines for the reconstruction of mutations and the huge number of genomic sequences are major problems for the analyses of mutations in the SARS-CoV-2 genome. As a solution, we advocate for the development of a centralized database of predicted mutations, which needs to be updated on a regular basis.
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Affiliation(s)
- Igor B. Rogozin
- Life Science Research Centre, Faculty of Science, University of Ostrava, 710 00 Ostrava, Czech Republic
| | - Andreu Saura
- Life Science Research Centre, Faculty of Science, University of Ostrava, 710 00 Ostrava, Czech Republic
| | - Eugenia Poliakov
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
| | - Anastassia Bykova
- Life Science Research Centre, Faculty of Science, University of Ostrava, 710 00 Ostrava, Czech Republic
| | - Abiel Roche-Lima
- Center for Collaborative Research in Health Disparities—RCMI Program, Medical Sciences Campus, University of Puerto Rico, San Juan 00936, Puerto Rico
| | - Youri I. Pavlov
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Vyacheslav Yurchenko
- Life Science Research Centre, Faculty of Science, University of Ostrava, 710 00 Ostrava, Czech Republic
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21
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Wang Z, Hu S, Popowski KD, Liu S, Zhu D, Mei X, Li J, Hu Y, Dinh PUC, Wang X, Cheng K. Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2. Nat Commun 2024; 15:2236. [PMID: 38472181 PMCID: PMC10933281 DOI: 10.1038/s41467-024-45628-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/24/2024] [Indexed: 03/14/2024] Open
Abstract
Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction becomes a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2, protecting the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates its deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protects hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercepts the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and shows comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as a broad-spectrum protectant against existing and emerging virus variants.
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Affiliation(s)
- Zhenzhen Wang
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, P.R. China.
- Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, 27606, USA.
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and North Carolina State University, Raleigh, NC, 27606, USA.
| | - Shiqi Hu
- Department of Biomedical Engineering, Columbia University, New York, New York, 10032, USA
| | - Kristen D Popowski
- Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, 27606, USA
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and North Carolina State University, Raleigh, NC, 27606, USA
| | - Shuo Liu
- Department of Biomedical Engineering, Columbia University, New York, New York, 10032, USA
| | - Dashuai Zhu
- Department of Biomedical Engineering, Columbia University, New York, New York, 10032, USA
| | - Xuan Mei
- Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, 27606, USA
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and North Carolina State University, Raleigh, NC, 27606, USA
| | - Junlang Li
- Xsome Biotech Inc., Raleigh, North Carolina, 27607, USA
| | - Yilan Hu
- Department of Biomedical Engineering, Columbia University, New York, New York, 10032, USA
| | - Phuong-Uyen C Dinh
- Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, 27606, USA
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and North Carolina State University, Raleigh, NC, 27606, USA
| | - Xiaojie Wang
- School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, P.R. China.
- Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun, 130118, P.R. China.
| | - Ke Cheng
- Department of Biomedical Engineering, Columbia University, New York, New York, 10032, USA.
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Al-Jamal H, Idriss S, Roufayel R, Abi Khattar Z, Fajloun Z, Sabatier JM. Treating COVID-19 with Medicinal Plants: Is It Even Conceivable? A Comprehensive Review. Viruses 2024; 16:320. [PMID: 38543686 PMCID: PMC10974729 DOI: 10.3390/v16030320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/15/2024] [Accepted: 02/18/2024] [Indexed: 05/23/2024] Open
Abstract
In 2020, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) challenged the world with a global outbreak that led to millions of deaths worldwide. Coronavirus disease 2019 (COVID-19) is the symptomatic manifestation of this virus, which can range from flu-like symptoms to utter clinical complications and even death. Since there was no clear medicine that could tackle this infection or lower its complications with minimal adverse effects on the patients' health, the world health organization (WHO) developed awareness programs to lower the infection rate and limit the fast spread of this virus. Although vaccines have been developed as preventative tools, people still prefer going back to traditional herbal medicine, which provides remarkable health benefits that can either prevent the viral infection or limit the progression of severe symptoms through different mechanistic pathways with relatively insignificant side effects. This comprehensive review provides scientific evidence elucidating the effect of 10 different plants against SARS-CoV-2, paving the way for further studies to reconsider plant-based extracts, rich in bioactive compounds, into more advanced clinical assessments in order to identify their impact on patients suffering from COVID-19.
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Affiliation(s)
- Hadi Al-Jamal
- Faculty of Public Health 3, Lebanese University, Tripoli 1100, Lebanon;
| | - Sara Idriss
- Laboratory of Applied Biotechnology (LBA3B), Azm Center for Research in Biotechnology and Its Applications, EDST, Lebanese University, Tripoli 1300, Lebanon;
| | - Rabih Roufayel
- College of Engineering and Technology, American University of the Middle East, Egaila 54200, Kuwait;
| | - Ziad Abi Khattar
- Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Tripoli P.O. Box 100, Lebanon;
| | - Ziad Fajloun
- Laboratory of Applied Biotechnology (LBA3B), Azm Center for Research in Biotechnology and Its Applications, EDST, Lebanese University, Tripoli 1300, Lebanon;
- Department of Biology, Faculty of Sciences 3, Campus Michel Slayman Ras Maska, Lebanese University, Tripoli 1352, Lebanon
| | - Jean-Marc Sabatier
- INP, Inst Neurophysiopathol, Aix-Marseille Université, CNRS, 13385 Marseille, France
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23
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Shokeen K, Kumar S. Newcastle disease virus regulates its replication by instigating oxidative stress-driven Sirtuin 7 production. J Gen Virol 2024; 105. [PMID: 38376490 DOI: 10.1099/jgv.0.001961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2024] Open
Abstract
Reactive oxygen species (ROS) accumulation inside the cells instigates oxidative stress, activating stress-responsive genes. The viral strategies for promoting stressful conditions and utilizing the induced host proteins to enhance their replication remain elusive. The present work investigates the impact of oxidative stress responses on Newcastle disease virus (NDV) pathogenesis. Here, we show that the progression of NDV infection varies with intracellular ROS levels. Additionally, the results demonstrate that NDV infection modulates the expression of oxidative stress-responsive genes, majorly sirtuin 7 (SIRT7), a NAD+-dependent deacetylase. The modulation of SIRT7 protein, both through overexpression and knockdown, significantly impacts the replication dynamics of NDV in DF-1 cells. The activation of SIRT7 is found to be associated with the positive regulation of cellular protein deacetylation. Lastly, the results suggested that NDV-driven SIRT7 alters NAD+ metabolism in vitro and in ovo. We concluded that the elevated expression of NDV-mediated SIRT7 protein with enhanced activity metabolizes the NAD+ to deacetylase the host proteins, thus contributing to high virus replication.
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Affiliation(s)
- Kamal Shokeen
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Sachin Kumar
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
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24
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Govednik T, Lainšček D, Kuhar U, Lachish M, Janežič S, Štrbenc M, Krapež U, Jerala R, Atlas D, Manček-Keber M. TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflammatory consequences. Antiviral Res 2024; 222:105806. [PMID: 38211737 DOI: 10.1016/j.antiviral.2024.105806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 12/23/2023] [Accepted: 01/08/2024] [Indexed: 01/13/2024]
Abstract
After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require caution. The spike protein of SARS-CoV-2 is an important target for both vaccines and therapeutics. The presence of disulfide bonds in the receptor binding domain (RBD) of the spike protein is essential for its binding to the human ACE2 receptor and cell entry. Here, we demonstrate that thiol-reducing peptides based on the active site of oxidoreductase thioredoxin 1, called thioredoxin mimetic (TXM) peptides, can prevent syncytia formation, SARS-CoV-2 entry into cells, and infection in a mouse model. We also show that TXM peptides inhibit the redox-sensitive HIV pseudotyped viral cell entry. These results support disulfide targeting as a common therapeutic strategy for treating infections caused by viruses using redox-sensitive fusion. Furthermore, TXM peptides exert anti-inflammatory properties by lowering the activation of NF-κB and IRF signaling pathways, mitogen-activated protein kinases (MAPKs) and lipopolysaccharide (LPS)-induced cytokines in mice. The antioxidant and anti-inflammatory effects of the TXM peptides, which also cross the blood-brain barrier, in combination with prevention of viral infections, may provide a beneficial clinical strategy to lower viral infections and mitigate severe consequences of COVID-19.
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Affiliation(s)
- Tea Govednik
- Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000, Ljubljana, Slovenia; Graduate School of Biomedicine, University of Ljubljana, 1000, Ljubljana, Slovenia
| | - Duško Lainšček
- Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000, Ljubljana, Slovenia; Centre of Excellence EN-FIST, 1000, Ljubljana, Slovenia
| | - Urška Kuhar
- Institute for Microbiology and Parasitology, Veterinary Faculty, University of Ljubljana, 1000, Ljubljana, Slovenia
| | - Marva Lachish
- Hebrew University of Jerusalem, Jerusalem, 91904, Israel
| | - Sandra Janežič
- National Laboratory of Health, Environment and Food, 2000, Maribor, Slovenia
| | - Malan Štrbenc
- Institute for Preclinical Sciences, Veterinary Faculty, University of Ljubljana, 1000, Ljubljana, Slovenia
| | - Uroš Krapež
- Institute of Poultry, Birds, Small Mammals and Reptiles, Veterinary Faculty, University of Ljubljana, 1000, Ljubljana, Slovenia
| | - Roman Jerala
- Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000, Ljubljana, Slovenia; Centre of Excellence EN-FIST, 1000, Ljubljana, Slovenia
| | - Daphne Atlas
- Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
| | - Mateja Manček-Keber
- Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000, Ljubljana, Slovenia; Centre of Excellence EN-FIST, 1000, Ljubljana, Slovenia.
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Cao M, Han Y, Feng T, Lu P, Wang Y, Sun Q, Zhao Z, Pan W. Impact of COVID-19 convalescence on pregnancy outcomes in patients undergoing IVF/ICSI during fresh ART cycles: a retrospective cohort study. Front Endocrinol (Lausanne) 2024; 14:1298995. [PMID: 38348053 PMCID: PMC10860335 DOI: 10.3389/fendo.2023.1298995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 12/20/2023] [Indexed: 02/15/2024] Open
Abstract
Objective The aim was to study the impact of coronavirus disease 2019 (COVID-19) convalescence on female fertility and laboratory and clinical outcomes in fresh assisted reproductive technology (ART) cycles. Methods In this retrospective cohort study, we analyzed data from 294 patients who had recovered from COVID-19 and who underwent fresh ART cycles between January and March 2023 (COVID-19 group). This group was compared with 631 patients who underwent similar ART cycles in the same period in 2022 but without having been infected with COVID-19 (non-COVID-19 group). The analysis focused on comparison of basic demographic characteristics and laboratory parameters of patients in each group. The primary outcome measure was the clinical pregnancy rate, which was examined to assess the impact of COVID-19 infection on the efficacy of ART treatment. Results Basal follicle-stimulating hormone (FSH) levels were significantly lower and antral follicle count (AFC) was markedly higher in the COVID-19 group compared to the non-COVID-19 group (P<0.001 and P=0.004, respectively). The predominant ovarian stimulation protocol in the COVID-19 group was GnRH antagonists (64.85%, P<0.001), with a reduced gonadotropin (Gn) dosage and duration in comparison to the non-COVID-19 group (P<0.05). Although the number of blastocysts formed was lower in the COVID-19 group (P=0.017), this group also exhibited a higher blastocyst freezing rate and a higher rate of high-quality embryos per retrieved oocyte (P<0.001 and P=0.023, respectively). Binary logistic regression analysis indicated that COVID-19 convalescence did not significantly impact clinical pregnancy rates in fresh transfer cycles (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 0.68-1.96, P=0.5874). However, smooth curve-fitting and threshold effect analysis revealed an age-related decline in clinical pregnancy rates in both groups, more pronounced in the COVID-19 group, for women aged over 38 years, with the likelihood of clinical pregnancy decreasing by 53% with each additional year of age (odds ratio [OR] = 0.81, 95% confidence interval [CI] = 0.61-1.08, P=0.1460; odds ratio [OR] = 0.47, 95% CI = 0.21-1.05, P=0.0647). Conclusions Our findings present no substantial evidence of adverse effects on clinical pregnancy outcomes in fresh ART cycles in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) during the period of convalescence from COVID-19. However, age emerges as a significant factor influencing these outcomes. Notably, for women above 38 years of age, the likelihood of clinical pregnancy in patients with a prior COVID-19 infection decreased by 53% with each additional year. This highlights the importance of considering maternal age, especially in the context of COVID-19, when evaluating the likelihood of successful pregnancy following ART treatments.
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Affiliation(s)
- Mingya Cao
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yan Han
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Tengfei Feng
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Peiyang Lu
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yue Wang
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Qingyun Sun
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhiming Zhao
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Wensen Pan
- Second Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
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Mosaffa-Jahromi M, Molavi Vardanjani H, Fuzimoto A, Hunter J, Lankarani KB, Pasalar M. Efficacy and safety of aniseed powder for treating gastrointestinal symptoms of COVID-19: a randomized, placebo-controlled trial. Front Pharmacol 2024; 15:1331177. [PMID: 38292939 PMCID: PMC10824915 DOI: 10.3389/fphar.2024.1331177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 01/08/2024] [Indexed: 02/01/2024] Open
Abstract
Background: Gastrointestinal symptoms are prevalent amongst patients with a confirmed diagnosis of COVID-19 and may be associated with an increased risk of disease severity. This trial aimed to evaluate the efficacy and safety of aniseed (Pimpinella anisum L.) powder as an add-on therapy to standard care for treating gastrointestinal symptoms experienced by adults with an acute SARS-CoV-2 infection. Methods: The study was a randomized parallel-group double-blinded placebo-controlled add-on therapy trial. Adults with an acute SARS-CoV-2 infection who did not require hospitalization and reported at least one gastrointestinal symptom in the preceding 48 h were assigned to either the aniseed or placebo group in a 1:4 ratio. All 225 participants (45 in the aniseed group and 180 in the placebo group) were instructed to use 25 g of powdered aniseed or placebo twice daily for 2 weeks. The primary outcomes were the proportion of patients who experienced an improvement of at least one point in the symptom score after adjusting for age group, gender, and time. Backwards stepwise logistic regression was applied to calculate the risk ratios. The clinical symptoms and adverse events were assessed at the beginning, 1 week later, and at the end of the trial (week two). Results: Participants in the aniseed group were significantly more likely to report symptom improvement for abdominal pain [adjusted risk ratio (RR):0.55; 95% confidence interval (CI): 0.46-0.72], anorexia (RR:0.62; 95% CI: 0.47-0.82), and diarrhea (RR:0.19; 95% CI: 0.12-0.30), but not nausea/vomiting (RR:0.87; 95% CI: 0.71-1.08) or bloating (RR:0.87; 95% CI: 0.72-1.05). Two participants in the aniseed group and three participants in the placebo group reported mild to moderate adverse events. Conclusion: This study showed that 2 weeks of aniseed powder containing trans-anethole (87%-94%) may help improve abdominal pain, anorexia, and diarrhea in COVID-19 patients. The findings align with the known biological, multitargeted activity of P. anisum and trans-anethole, which includes inhibiting SARS-CoV-2 along with other anti-infective, anti-inflammatory, antioxidant, hepatoprotective, and anti-dysbiosis properties. Multicenter trials with larger sample sizes and longer follow-up are warranted to confirm these findings. Clinical Trial Registration: Iranian Registry of Clinical Trials (IRCT20120506009651N3).
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Affiliation(s)
- Maryam Mosaffa-Jahromi
- Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Molavi Vardanjani
- Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | | | | | - Mehdi Pasalar
- Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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27
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Shajahan SR, Kumar S, Ramli MDC. Unravelling the connection between COVID-19 and Alzheimer's disease: a comprehensive review. Front Aging Neurosci 2024; 15:1274452. [PMID: 38259635 PMCID: PMC10800459 DOI: 10.3389/fnagi.2023.1274452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 12/14/2023] [Indexed: 01/24/2024] Open
Abstract
Currently, there exists a limited comprehension regarding the correlation between COVID-19 and Alzheimer's disease (AD). To elucidate the interrelationship and its impact on outcomes, a comprehensive investigation was carried out utilising time-unrestricted searches of reputable databases such as Scopus, PubMed, Web of Science, and Google Scholar. Our objective was to evaluate the impact of various medical conditions on severe COVID-19-related events. We focused on identifying and analysing articles that discussed the clinical characteristics of COVID-19 patients, particularly those pertaining to severe events such as ICU admission, mechanical ventilation, pneumonia, mortality and acute respiratory distress syndrome (ARDS) a serious lung condition that causes low blood oxygen. Through careful data analysis and information gathering, we tried to figure out how likely it was that people with conditions, like AD, would have serious events. Our research investigated potential mechanisms that link AD and COVID-19. The ability of the virus to directly invade the central nervous system and the role of ACE-2 receptors were investigated. Furthermore, the OAS1 gene served as the genetic link between AD and COVID-19. In the context of COVID-19, our findings suggest that individuals with AD may be more susceptible to experiencing severe outcomes. Consequently, it is crucial to provide personalised care and management for this demographic. Further investigation is required to attain a comprehensive comprehension of the intricate correlation between Alzheimer's disease and COVID-19, as well as its ramifications for patient outcomes.
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Affiliation(s)
- Shah Rezlan Shajahan
- School of Graduate Studies, Management and Science University, Shah Alam, Selangor, Malaysia
| | - Suresh Kumar
- Faculty of Health and Life Sciences, Management and Science University, Shah Alam, Selangor, Malaysia
| | - Muhammad Danial Che Ramli
- Faculty of Health and Life Sciences, Management and Science University, Shah Alam, Selangor, Malaysia
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28
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Sotnikova-Meleshkina ZV, Yatsyk YO, Bobrova OV, Kryvonos KA. The influence of vitamin and mineral consumption on the course of coronavirus disease (COVID-19). WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2024; 77:1086-1092. [PMID: 39008602 DOI: 10.36740/wlek202405132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/17/2024]
Abstract
OBJECTIVE Aim: The study of the role of micronutrients in the prevention of the severe course of the coronavirus disease. PATIENTS AND METHODS Materials and Methods: In order to fulfill the task, there was conducted an analytical review of medical and biological publications in English in the electronic databases PubMed Medline of the US National Library of Medicine (NLM), Embase, Cochrane Database of Systematic Reviews for the period from 2015 to November 2023, where included 50 published articles, 28 preprints and 109 trials. In the course of the study, the bibliographic-semantic research method was used according to the "Preferred Reporting Elements for Systematic Reviews and Meta-Analyses" (PRISMA) protocol. According to this protocol, identified literary sources were sequentially analyzed by title, keywords, abstract and full text of articles. Based on the results of 16 searches, 2650 articles from PubMed, Cochrane Database of Systematic Reviews and Embase, 3162 articles from preprint servers and 237 trials were rejected. In the final article synthesis, we included 50 published articles, 28 preprints, and 109 trials. CONCLUSION Conclusions: The most effective in preventing complications of the coronavirus disease are vitamins A, D, E, K, C, B3, B6, B9, B12 and such mineral substances as Mg, Se and Zn. The consumption of appropriate bioactive complexes and source products can be considered a clinically and economically effective strategy for the prevention of a severe course of the coronavirus disease.
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Bastin A, Abbasi F, Roustaei N, Abdesheikhi J, Karami H, Gholamnezhad M, Eftekhari M, Doustimotlagh A. Severity of oxidative stress as a hallmark in COVID-19 patients. Eur J Med Res 2023; 28:558. [PMID: 38049886 PMCID: PMC10696844 DOI: 10.1186/s40001-023-01401-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 09/27/2023] [Indexed: 12/06/2023] Open
Abstract
INTRODUCTION Understanding the mechanisms and identifying effective treatments for the COVID-19 outbreak are imperative. Therefore, this study aimed to assess the antioxidant status and oxidative stress parameters as potential pivotal mechanisms in asymptomatic, non-severe, and severe COVID-19 patients. METHODS This study is a case-control study that was performed on patients referred to the Persian Gulf Martyrs Hospital of Bushehr University of Medical Sciences, Bushehr, Iran, from May 2021 to September 2021. A total of 600 COVID-19 patients (non-severe and severe group) and 150 healthy volunteers of the same age and sex were selected during the same period. On the first day of hospitalization, 10 ml of venous blood was taken from subjects. Then, hematological, biochemical, serological, antioxidant and oxidative stress parameters were determined. RESULTS Our results indicated that ESR, CRP, AST, ALT, and LDH significantly augmented in the severe group as compared to the non-severe and normal groups (P ≤ 0.05). It was observed that the levels of FRAP, G6PD activity, and SOD activity significantly reduced in the non-severe patients in comparison with the severe and normal groups (P ≤ 0.05). We found that MDA content and NO metabolite markedly increased in severe patients as compared to the non-severe group. CONCLUSIONS Taken together, it seems that the balance between antioxidants and oxidants was disturbed in COVID-19 patients in favor of oxidant markers. In addition, this situation caused more aggravation in severe patients as compared to the non-severe group.
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Affiliation(s)
- Alireza Bastin
- Clinical Research Development Center, "The Persian Gulf Martyrs" Hospital, Bushehr University of Medical Sciences, Bushehr, Iran
- Department of Clinical Biochemistry, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Fatemeh Abbasi
- Department of Infectious Disease, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Narges Roustaei
- Department of Biostatistics and Epidemiology, School of Health, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Jahangir Abdesheikhi
- Department of Clinical Immunology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Hossein Karami
- Clinical Research Development Center, "The Persian Gulf Martyrs" Hospital, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Mohammad Gholamnezhad
- Department of Infectious Disease, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Mahdieh Eftekhari
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Amirhossein Doustimotlagh
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
- Department of Clinical Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
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Li D, Cao W, Zhou Q, Wu X, Song X, Qin H. COVID-19 and primary wound healing: A new insights and advance. Int Wound J 2023; 20:4422-4428. [PMID: 37488776 PMCID: PMC10681437 DOI: 10.1111/iwj.14324] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 07/11/2023] [Indexed: 07/26/2023] Open
Abstract
With the outbreak and pandemic of coronavirus disease-2019 (COVID-19), a huge number of people died of it. Apart from lung injuries, multiple organs have been confirmed to be impaired. In COVID-19 time, primary wound healing processes always prolong, however, its possible underlying mechanisms are still unclear. Therefore, to overcome this clinical problem, clarifying its underlying mechanisms clearly is necessary and urgently needed. In this review, we summarized that COVID-19 can prolong primary wound healing by inducing excessive inflammation and oxidative stress, disturbing immune system and haematological system, as well as influencing the functions and viability of epidermal stem cells (ESCs). Otherwise, we summarized that the strict control measures of blocking up COVID-19 pandemic can also have side effects on primary wound healing process.
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Affiliation(s)
- Danyi Li
- Department of OphthalmologyJiading District Central Hospital Affiliated Shanghai University of Medicine & Health SciencesShanghaiChina
| | - Wenjie Cao
- Department of OphthalmologyJiading District Central Hospital Affiliated Shanghai University of Medicine & Health SciencesShanghaiChina
| | - Qun Zhou
- Department of OphthalmologyJiading District Central Hospital Affiliated Shanghai University of Medicine & Health SciencesShanghaiChina
| | - Xiaomin Wu
- Department of OphthalmologyJiading District Central Hospital Affiliated Shanghai University of Medicine & Health SciencesShanghaiChina
| | - Xiayun Song
- Department of OphthalmologyJiading District Central Hospital Affiliated Shanghai University of Medicine & Health SciencesShanghaiChina
| | - Haofang Qin
- Department of OphthalmologyJiading District Central Hospital Affiliated Shanghai University of Medicine & Health SciencesShanghaiChina
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Viçozzi GP, de Oliveira Pereira FS, da Silva RS, Leal JG, Sarturi JM, Nogara PA, Rodrigues OED, Teixeira da Rocha JB, Ávila DS. In silico evidences of Mpro inhibition by a series of organochalcogen-AZT derivatives and their safety in Caenorhabditis elegans. J Trace Elem Med Biol 2023; 80:127297. [PMID: 37716209 DOI: 10.1016/j.jtemb.2023.127297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 08/02/2023] [Accepted: 08/29/2023] [Indexed: 09/18/2023]
Abstract
BACKGROUND The new coronavirus (SARS-CoV-2) pandemic emerged in 2019 causing millions of deaths. Vaccines were quickly developed and made available in 2021. Despite the availability of vaccines, some subjects refuse to take the immunizing or present comorbities, therefore developing serious cases of COVID-19, which makes necessary the development of antiviral drugs. Previous studies have demonstrated that ebselen, a selenium-containing molecule, can inhibit SARS-CoV-2 Mpro. In addition, selenium is a trace element that has antiviral and anti-inflammatory properties. Zidovudine (AZT) has been widely used against HIV infections and its action against SARS-CoV-2 may be altered by the structural modification with organochalcogen moieties, but this hypothesis still needs to be tested. METHODS In the present work we evaluated the Mpro inhibition capacity (in silico), the safety and antioxidant effect of six organochalcogen AZT-derivatives using the free-living nematode Caenorhabditis elegans, through acute (30 min) and chronic (48) exposure protocols. RESULTS We observed that the molecules were safe at a concentration range of 1-500 µM and did not alter any toxicological endpoint evaluated. Furthermore, the molecules are capable to decrease the ROS formation stimulated by hydrogen peroxide, to modulate the expression of important antioxidant enzymes such superoxide-dismutase-3 and glutathione S-transferese-4 and to stimulate the translocation of the DAF-16 to the cell nucleus. In addition, the molecules did not deplete thiol groups, which reinforces their safety and contribution to oxidative stress resistance. CONCLUSIONS We have found that compounds S116l (a Tellurium AZT-derivative) and S116h (a Selenium-AZT derivative) presented more promising effects both in silico and in vivo, being strong candidates for further in vivo studies.
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Affiliation(s)
- Gabriel Pedroso Viçozzi
- Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCE), Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970 Uruguaiana, RS, Brazil; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil
| | - Flávia Suelen de Oliveira Pereira
- Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCE), Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970 Uruguaiana, RS, Brazil
| | - Rafael Santos da Silva
- LabSelen-NanoBio - Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, Brazil
| | - Julliano Guerin Leal
- LabSelen-NanoBio - Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, Brazil
| | - Joelma Menegazzi Sarturi
- LabSelen-NanoBio - Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, Brazil
| | - Pablo Andrei Nogara
- Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil; Instituto Federal de Educação, Ciência e Tecnologia Sul-rio-grandense (IFSul), Av. Leonel de Moura Brizola, 2501, 96418-400 Bagé, RS, Brazil
| | | | - João Batista Teixeira da Rocha
- Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil
| | - Daiana Silva Ávila
- Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCE), Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970 Uruguaiana, RS, Brazil; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil.
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Au TY, Assavarittirong C, Benjamin S, Wiśniewski OW. Is there a correlation between antibiotic use and the severity or post-infection conditions of COVID-19 and other viral infections? Clin Exp Med 2023; 23:4123-4128. [PMID: 37653183 DOI: 10.1007/s10238-023-01171-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 08/12/2023] [Indexed: 09/02/2023]
Abstract
Antibiotics are one of the most frequently prescribed medications in modern medicine; besides treating bacterial infections, they may often be utilized for prophylactic purposes, including during select viral infections. It has been shown that 74.9% of COVID-19 patients received antibiotics as a part of their treatment regimen during the pandemic. However, studies suggest that the actual incidence of bacterial coinfection was relatively uncommon with a mere 3.5% of overall cases reported. A recent study revealed that antibiotic administration would not improve disease progression or shorten the length of hospitalization in COVID-19 patients; additionally, some antibiotics, such as linezolid, promote the production of free radicals that might be responsible for exacerbated clinical symptoms during and post-infection. Notably, antibiotic use disturbs the normal gut microbiome, and this interference impedes antiviral immune response enhancing severity and susceptibility to a list of viral infections. Thus, resultant augmented severity of these infections may be a consequence of higher susceptibility to respiratory viral co-infection.
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Affiliation(s)
- Tsz Yuen Au
- North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees, UK.
- Center for Medical Education in English, Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland.
| | - Chanika Assavarittirong
- Internal Medicine Residency Program, UHS Southern California Medical Education Consortium, Temecula, CA, USA
- Center for Medical Education in English, Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Shamiram Benjamin
- Faculty of Internal Medicine, Dignity Health East Valley, Chandler, AZ, USA
- Center for Medical Education in English, Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Oskar Wojciech Wiśniewski
- Faculty of Health Sciences, Calisia University, Kalisz, Poland
- Department of Cardiology-Intensive Therapy and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
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Primo MGS, da Silva LAA, de Carvalho VBL, de Azevedo MAF, Monteiro NVDN, Mendes VR, da Silva JKM, Oliveira ASDSS, Brito AKDS, Sales ALDCC, Mallet JRDS, Parente JML, de Matos Neto EM, Ferreira PMP, Arcanjo DDR, Martins MDCDCE. Relationship among Dietary Intake of Vitamin E, Lipid Peroxidation Markers, and C-Reactive Protein in Flu-Like Patients Diagnosed with COVID-19. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:8889213. [PMID: 39263681 PMCID: PMC11390186 DOI: 10.1155/2023/8889213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 07/05/2023] [Accepted: 09/30/2023] [Indexed: 09/13/2024]
Abstract
Objective This research aimed to assess the intake of vitamin E and its relationship with lipid peroxidation markers and C-reactive protein levels in patients with flu symptoms and COVID-19 diagnosis. Methods A cross-sectional study with 121 patients of both sexes assisted at two basic health units in the city of Teresina, Piauí, with COVID-19 diagnosis confirmed through real-time reverse transcription polymerase chain reaction, was performed between the 3rd and 7th days of flu symptoms. The global nutritional status and the measurement of waist circumference were assessed according to the World Health Organization recommendations. The dietary energy intake, macronutrients, and vitamin E consumption were assessed through the 24 hr food recall method. The malondialdehyde plasmatic concentration (MDA) was measured through the method of thiobarbituric acid-reactive substances. Myeloperoxidase (MPO) was assessed through the oxidation speed of the o-dianisidine substrate in the presence of hydrogen peroxide. C-reactive protein (CRP) levels were measured by a high-sensitivity immunoturbidimetry method. Results The most common symptoms reported by the participants were sore throat, fever, and cough. Regarding the global nutritional status evaluation, the majority of the sample had overweight. The dietary intake of vitamin E was 100% inadequate and presented a mild correlation (r = 0.197) with MDA, a redox status marker. No correlation was observed among MPO, CRP, and the dietary intake of vitamin E. Conclusion The dietary intake of vitamin E was related to MDA as the marker of redox status.
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Sutaria SR, Morris JD, Xie Z, Cooke EA, Silvers SM, Long GA, Balcom D, Marimuthu S, Parrish LW, Aliesky H, Arnold FW, Huang J, Fu XA, Nantz MH. A feasibility study on exhaled breath analysis using UV spectroscopy to detect COVID-19. J Breath Res 2023; 18:016004. [PMID: 37875100 PMCID: PMC10620812 DOI: 10.1088/1752-7163/ad0646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 09/14/2023] [Accepted: 10/24/2023] [Indexed: 10/26/2023]
Abstract
A 23-subject feasibility study is reported to assess how UV absorbance measurements on exhaled breath samples collected from silicon microreactors can be used to detect COVID-19. The silicon microreactor technology chemoselectively preconcentrates exhaled carbonyl volatile organic compounds and subsequent methanol elution provides samples for analysis. The underlying scientific rationale that viral infection will induce an increase in exhaled carbonyls appears to be supported by the results of the feasibility study. The data indicate statistically significant differences in measured UV absorbance values between healthy and symptomatic COVID-19 positive subjects in the wavelength range from 235 nm to 305 nm. Factors such as subject age were noted as potential confounding variables.
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Affiliation(s)
- Saurin R Sutaria
- Departments of Chemistry, University of Louisville, Louisville, KY 40292, United States of America
| | - James D Morris
- Chemical Engineering, University of Louisville, Louisville, KY 40292, United States of America
| | - Zhenzhen Xie
- Chemical Engineering, University of Louisville, Louisville, KY 40292, United States of America
| | - Elizabeth A Cooke
- Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY 40292, United States of America
| | - Shavonne M Silvers
- Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY 40292, United States of America
| | - Grace A Long
- Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY 40292, United States of America
| | - Dawn Balcom
- Division of Infectious Diseases, Department of Medicine, University of Louisville, Louisville, KY 40292, United States of America
| | - Subathra Marimuthu
- Division of Infectious Diseases, Department of Medicine, University of Louisville, Louisville, KY 40292, United States of America
| | - Leslie W Parrish
- Division of Infectious Diseases, Department of Medicine, University of Louisville, Louisville, KY 40292, United States of America
| | - Holly Aliesky
- Division of Infectious Diseases, Department of Medicine, University of Louisville, Louisville, KY 40292, United States of America
| | - Forest W Arnold
- Division of Infectious Diseases, Department of Medicine, University of Louisville, Louisville, KY 40292, United States of America
| | - Jiapeng Huang
- Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY 40292, United States of America
| | - Xiao-An Fu
- Chemical Engineering, University of Louisville, Louisville, KY 40292, United States of America
| | - Michael H Nantz
- Departments of Chemistry, University of Louisville, Louisville, KY 40292, United States of America
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Liu S, Zhao Y, Feng X, Xu H. SARS-CoV-2 infection threatening intestinal health: A review of potential mechanisms and treatment strategies. Crit Rev Food Sci Nutr 2023; 63:12578-12596. [PMID: 35894645 DOI: 10.1080/10408398.2022.2103090] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The outbreak of the COVID-19 pandemic has brought great problems to mankind, including economic recession and poor health. COVID-19 patients are frequently reported with gastrointestinal symptoms such as diarrhea and vomiting in clinical diagnosis. Maintaining intestinal health is the key guarantee to maintain the normal function of multiple organs, otherwise it will be a disaster. Therefore, the purpose of this review was deeply understanded the potential mechanism of SARS-CoV-2 infection threatening intestinal health and put forward reasonable treatment strategies. Combined with the existing researches, we summarized the mechanism of SARS-CoV-2 infection threatening intestinal health, including intestinal microbiome disruption, intestinal barrier dysfunction, intestinal oxidative stress and intestinal cytokine storm. These adverse intestinal events may affect other organs through the circulatory system or aggravate the course of the disease. Typically, intestinal disadvantage may promote the progression of SARS-CoV-2 through the gut-lung axis and increase the disease degree of COVID-19 patients. In view of the lack of specific drugs to inhibit SARS-CoV-2 replication, the current review described new strategies of probiotics, prebiotics, postbiotics and nutrients to combat SARS-CoV-2 infection and maintain intestinal health. To provide new insights for the prevention and treatment of gastrointestinal symptoms and pneumonia in patients with COVID-19.
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Affiliation(s)
- Shanji Liu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Yu Zhao
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Xiaoyan Feng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Hengyi Xu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
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Grand RJ. SARS-CoV-2 and the DNA damage response. J Gen Virol 2023; 104:001918. [PMID: 37948194 PMCID: PMC10768691 DOI: 10.1099/jgv.0.001918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 10/27/2023] [Indexed: 11/12/2023] Open
Abstract
The recent coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by respiratory distress, multiorgan dysfunction and, in some cases, death. The virus is also responsible for post-COVID-19 condition (commonly referred to as 'long COVID'). SARS-CoV-2 is a single-stranded, positive-sense RNA virus with a genome of approximately 30 kb, which encodes 26 proteins. It has been reported to affect multiple pathways in infected cells, resulting, in many cases, in the induction of a 'cytokine storm' and cellular senescence. Perhaps because it is an RNA virus, replicating largely in the cytoplasm, the effect of SARS-Cov-2 on genome stability and DNA damage responses (DDRs) has received relatively little attention. However, it is now becoming clear that the virus causes damage to cellular DNA, as shown by the presence of micronuclei, DNA repair foci and increased comet tails in infected cells. This review considers recent evidence indicating how SARS-CoV-2 causes genome instability, deregulates the cell cycle and targets specific components of DDR pathways. The significance of the virus's ability to cause cellular senescence is also considered, as are the implications of genome instability for patients suffering from long COVID.
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Affiliation(s)
- Roger J. Grand
- Institute for Cancer and Genomic Science, The Medical School, University of Birmingham, Birmingham, UK
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Hegazy GE, Abu-Serie MM, Soliman NA, Teleb M, Abdel-Fattah YR. Superior anti-pulmonary viral potential of Natrialba sp. M6-producing surfactin and C50 carotenoid pigment with unveiling its action modes. Virol J 2023; 20:249. [PMID: 37904234 PMCID: PMC10614327 DOI: 10.1186/s12985-023-02215-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Accepted: 10/20/2023] [Indexed: 11/01/2023] Open
Abstract
BACKGROUND Respiratory viruses, particularly adenoviruses (ADV), influenza A virus (e.g., H1N1), and coronaviruses (e.g., HCoV-229E and SARS-CoV-2) pose a global public health problem. Therefore, developing natural wide-spectrum antiviral compounds for disrupting the viral life cycle with antioxidant activity provides an efficient treatment approach. Herein, biosurfactant (Sur) and C50 carotenoid pigment (Pig) of haloalkaliphilic archaeon Natrialba sp. M6 which exhibited potent efficacy against hepatitis and anti-herpes simplex viruses, were investigated against pulmonary viruses. METHODS The cytotoxicity of the extracted Sur and Pig was examined on susceptible cell lines for ADV, HIN1, HCoV-229E, and SARS-CoV-2. Their potential against the cytopathic activity of these viruses was detected with investigating the action modes (including, virucidal, anti-adsorption, and anti-replication), unveiling the main mechanisms, and using molecular docking analysis. Radical scavenging activity was determined and HPLC analysis for potent extract (Sur) was performed. RESULTS All current investigations stated higher anti-pulmonary viruses of Sur than Pig via mainly virucidal and/or anti-replicative modes. Moreover, Sur had stronger ADV's capsid protein binding, ADV's DNA polymerase inhibition, suppressing hemagglutinin and neuraminidase of H1N1, and inhibiting chymotrypsin-like (3CL) protease of SARS-CoV-2, supporting with in-silico analysis, as well as radical scavenging activity than Pig. HPLC analysis of Sur confirmed the predominate presence of surfactin in it. CONCLUSION This study declared the promising efficacy of Sur as an efficient pharmacological treatment option for these pulmonary viruses and considered as guide for further in vivo research.
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Affiliation(s)
- Ghada E Hegazy
- National Institute of Oceanography and Fisheries, NIOF, Cairo, Egypt.
- Bioprocess Development Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications, Alexandria, Egypt.
| | - Marwa M Abu-Serie
- Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications, Alexandria, Egypt.
| | - Nadia A Soliman
- Bioprocess Development Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications, Alexandria, Egypt.
| | - Mohamed Teleb
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Yasser R Abdel-Fattah
- Bioprocess Development Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications, Alexandria, Egypt.
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Georgieva E, Ananiev J, Yovchev Y, Arabadzhiev G, Abrashev H, Abrasheva D, Atanasov V, Kostandieva R, Mitev M, Petkova-Parlapanska K, Karamalakova Y, Koleva-Korkelia I, Tsoneva V, Nikolova G. COVID-19 Complications: Oxidative Stress, Inflammation, and Mitochondrial and Endothelial Dysfunction. Int J Mol Sci 2023; 24:14876. [PMID: 37834324 PMCID: PMC10573237 DOI: 10.3390/ijms241914876] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 09/28/2023] [Accepted: 09/28/2023] [Indexed: 10/15/2023] Open
Abstract
SARS-CoV-2 infection, discovered and isolated in Wuhan City, Hubei Province, China, causes acute atypical respiratory symptoms and has led to profound changes in our lives. COVID-19 is characterized by a wide range of complications, which include pulmonary embolism, thromboembolism and arterial clot formation, arrhythmias, cardiomyopathy, multiorgan failure, and more. The disease has caused a worldwide pandemic, and despite various measures such as social distancing, various preventive strategies, and therapeutic approaches, and the creation of vaccines, the novel coronavirus infection (COVID-19) still hides many mysteries for the scientific community. Oxidative stress has been suggested to play an essential role in the pathogenesis of COVID-19, and determining free radical levels in patients with coronavirus infection may provide an insight into disease severity. The generation of abnormal levels of oxidants under a COVID-19-induced cytokine storm causes the irreversible oxidation of a wide range of macromolecules and subsequent damage to cells, tissues, and organs. Clinical studies have shown that oxidative stress initiates endothelial damage, which increases the risk of complications in COVID-19 and post-COVID-19 or long-COVID-19 cases. This review describes the role of oxidative stress and free radicals in the mediation of COVID-19-induced mitochondrial and endothelial dysfunction.
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Affiliation(s)
- Ekaterina Georgieva
- Department of General and Clinical Pathology, Forensic Medicine, Deontology and Dermatovenerology, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria;
| | - Julian Ananiev
- Department of General and Clinical Pathology, Forensic Medicine, Deontology and Dermatovenerology, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria;
| | - Yovcho Yovchev
- Department of Surgery and Anesthesiology, University Hospital “Prof. Dr. St. Kirkovich”, 6000 Stara Zagora, Bulgaria; (Y.Y.); (G.A.)
| | - Georgi Arabadzhiev
- Department of Surgery and Anesthesiology, University Hospital “Prof. Dr. St. Kirkovich”, 6000 Stara Zagora, Bulgaria; (Y.Y.); (G.A.)
| | - Hristo Abrashev
- Department of Vascular Surgery, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria;
| | - Despina Abrasheva
- II Department of Internal Medicine Therapy: Cardiology, Rheumatology, Hematology and Gastroenterology, Medical Faculty, Trakia University, 6000 Stara Zagora, Bulgaria;
| | - Vasil Atanasov
- Forensic Toxicology Laboratory, Military Medical Academy, 3 G. Sofiiski, 1606 Sofia, Bulgaria; (V.A.); (R.K.)
| | - Rositsa Kostandieva
- Forensic Toxicology Laboratory, Military Medical Academy, 3 G. Sofiiski, 1606 Sofia, Bulgaria; (V.A.); (R.K.)
| | - Mitko Mitev
- Department of Diagnostic Imaging, University Hospital “Prof. Dr. St. Kirkovich”, 6000 Stara Zagora, Bulgaria;
| | - Kamelia Petkova-Parlapanska
- Department of Medical Chemistry and Biochemistry, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria; (K.P.-P.); (Y.K.)
| | - Yanka Karamalakova
- Department of Medical Chemistry and Biochemistry, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria; (K.P.-P.); (Y.K.)
| | - Iliana Koleva-Korkelia
- Department of Obstetrics and Gynaecology Clinic, University Hospital “Prof. St. Kirkovich”, 6000 Stara Zagora, Bulgaria;
| | - Vanya Tsoneva
- Department of Propaedeutics of Internal Medicine and Clinical Laboratory, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria;
| | - Galina Nikolova
- Department of Medical Chemistry and Biochemistry, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria; (K.P.-P.); (Y.K.)
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Galindo-Andúgar MA, Arias Arias Á, Alfonso García Guerra J, Fernández Visier I, Manuel Fernández Ibáñez J, Bellido Maldonado A. Impact of N-Acetylcysteine in the mortality of patients hospitalized with COVID-19: a retrospective cohort study. Rev Clin Esp 2023; 223:479-485. [PMID: 37482215 DOI: 10.1016/j.rceng.2023.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 07/08/2023] [Indexed: 07/25/2023]
Abstract
INTRODUCTION AND AIM N-Acetylcysteine has been proposed for the treatment of COVID-19 thanks to its mucolytic, antioxidant and anti-inflammatory effects. Our aim is to evaluate its effect on patients admitted with COVID-19 in mortality terms. MATERIAL AND METHODS Retrospective single-center cohort study. All patients admitted to our hospital for COVID-19 from March to April 2020 have been considered. RESULTS A total of 378 patients were included, being 196 (51.9%) men, with an average age of 73.3±14.5 years. 52.6% (199) received treatment with N-Acetylcysteine. More than 70% presented coughs, fever, and/or dyspnea. The global hospital mortality was 26.7%. A multivariate analysis through logistic regression identified the age of patients [older than 80; OR: 8.4 (CI95%:3-23.4)], a moderate or severe radiologic affectation measured by the RALE score [OR:7.3 (CI95%:3.2-16.9)], the tobacco consumption [OR:2.8 (CI95%:1.3-6.1)] and previous arrhythmia [OR 2.8 (CI95%: 1.3-6.2)] as risk factor that were independently associated with mortality during the admission. The treatment with N-Acetylcysteine was identified as a protective factor [OR: 0.57 (CI95%: 0.31-0.99)]. Asthma also seems to have a certain protective factor although it was not statistically significant in our study [OR: 0.19 (CI95%: 0.03-1.06)]. CONCLUSIONS Patients with COVID-19 treated with N-acetylcysteine have presented a lower mortality and a better evolution in this study. Future prospective studies or randomized clinical trials must confirm the impact of N-Acetylcysteine on COVID-19 patients.
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Affiliation(s)
- M A Galindo-Andúgar
- Servicio de Medicina Interna. Hospital General La Mancha Centro, Alcázar de San Juan (C. Real), Spain.
| | - Á Arias Arias
- Unidad de Docencia, Investigación y Formación, Hospital General La Mancha Centro, Alcázar de San Juan (C. Real), Spain
| | - J Alfonso García Guerra
- Sección de Neumología, Hospital General La Mancha Centro, Alcázar de San Juan (C. Real), Spain
| | - I Fernández Visier
- Sección de Aparato Digestivo, Hospital General La Mancha Centro, Alcázar de San Juan (C. Real), Spain
| | | | - A Bellido Maldonado
- Sección de Neumología, Hospital General La Mancha Centro, Alcázar de San Juan (C. Real), Spain
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Tang Y, Li Y, Wang Z, Huang W, Fan Q, Liu B. In Situ Noninvasive Observation of Nitric Oxide Fluctuation in SARS-CoV-2 Infection In Vivo by Organic Near-Infrared-II Fluorescent Molecular Nanoprobes. ACS NANO 2023; 17:18299-18307. [PMID: 37712857 DOI: 10.1021/acsnano.3c05410] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/16/2023]
Abstract
The pathogenesis understanding of SARS-CoV-2 infection is crucial to prevent the rampant spread of COVID-19 and its contribution to deterioration in health, even death. Nitric oxide (NO), a crucial molecule involved in signal transduction and cytotoxicity, is a possible key regulator in the occurrence and development of COVID-19. However, understanding the pathogenesis of NO in SARS-CoV-2 infection is still in its infancy due to the lack of suitable in situ monitoring probes of NO fluctuation in the complex SARS-CoV-2 infection environment in deep lung tissues. Herein, we developed an activatable near-infrared-II fluorescent molecular nanoprobe (OSNP) that uncages high-resolution and deep-tissue-penetrating near-infrared-II fluorescence signal in specific response to NO for in situ and noninvasive visualization of NO fluctuation in a SARS-CoV-2 infection mouse model in lung tissues. In vivo visualization revealed that the NO level is a positive relationship with SARS-CoV-2 infection progress. With the assistance of immuno-histochemical analyses, we uncovered the NO-involved pathological mechanism, that being the improved NO level is associated with an increase in inducible NO synthase rather than endothelial NO synthase. Our study not only provides the example of a near-infrared-II fluorescent imaging of NO in SARS-CoV-2 infection but also provides opportunities to uncover tunderlying pathomechanism of NO for SARS-Cov-2 infections.
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Affiliation(s)
- Yufu Tang
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore
| | - Yuanyuan Li
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Zhen Wang
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Wei Huang
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Quli Fan
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Bin Liu
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore
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Dave B, Shah KC, Chorawala MR, Shah N, Patel P, Patel S, Shah P. Molnupiravir: an antiviral drug against COVID-19. Arch Virol 2023; 168:252. [PMID: 37710056 DOI: 10.1007/s00705-023-05881-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 05/28/2023] [Indexed: 09/16/2023]
Abstract
SARS-CoV-2, the virus responsible for COVID-19, has caused numerous deaths worldwide and poses significant challenges. Researchers have recently studied a new antiviral drug called molnupiravir for treating COVID-19. This review examines the causes and immunopathogenesis of COVID-19, as well as the role of molnupiravir in its treatment. Molnupiravir is a prodrug of β-D-N4-hydroxyctytidine (NHC) and has demonstrated activity against various viruses, including MERS-CoV, SARS-CoV, SARS-CoV-2, and influenza virus. The active form of molnupiravir, NHC triphosphate, acts as a nucleoside analog that disrupts viral replication by causing mutations in the viral RNA, thereby inhibiting viral growth. This review summarizes the results of multiple clinical trials that have evaluated the effectiveness of molnupiravir against SARS-CoV-2 and its variants. Animal studies have also shown that molnupiravir significantly reduces the viral load and prevents transmission to other animals. Overall, molnupiravir has demonstrated strong efficacy and reasonable safety, reducing hospitalization rates by nearly 50% among COVID-19-positive individuals at risk of complications. Patients in clinical settings have tolerated molnupiravir well and experienced positive outcomes, such as clearance of viral RNA, decreased viral load, and reduced hospitalization rates. Additionally, compared to a placebo, molnupiravir has been associated with lower mortality rates. Therefore, molnupiravir can be a beneficial drug to treat patients suffering from SARS-CoV-2, and further studies can provide more information about its safety and efficacy.
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Affiliation(s)
- Bhavarth Dave
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, Gujarat, 380 009, India
| | - Kashvi C Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, Gujarat, 380 009, India
| | - Mehul R Chorawala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, Gujarat, 380 009, India.
| | - Nirav Shah
- Department of Pharmaceutics, SAL Institute of Pharmacy, Sola, Ahmedabad, Gujarat, 380015, India
| | - Pranjal Patel
- Department of Pharmaceutics, SAL Institute of Pharmacy, Sola, Ahmedabad, Gujarat, 380015, India
| | - Suzan Patel
- Department of Pharmaceutics, SAL Institute of Pharmacy, Sola, Ahmedabad, Gujarat, 380015, India
| | - Palak Shah
- Department of Pharmacology and Pharmacy Practice, K. B. Institute of Pharmaceutical Education and Research, Gh-6, Sector-23, Gandhinagar, Gujarat, 382023, India
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Thakur A, Sharma V, Averbek S, Liang L, Pandya N, Kumar G, Cili A, Zhang K. Immune landscape and redox imbalance during neurological disorders in COVID-19. Cell Death Dis 2023; 14:593. [PMID: 37673862 PMCID: PMC10482955 DOI: 10.1038/s41419-023-06102-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 08/13/2023] [Accepted: 08/22/2023] [Indexed: 09/08/2023]
Abstract
The outbreak of Coronavirus Disease 2019 (COVID-19) has prompted the scientific community to explore potential treatments or vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the illness. While SARS-CoV-2 is mostly considered a respiratory pathogen, several neurological complications have been reported, raising questions about how it may enter the Central Nervous System (CNS). Receptors such as ACE2, CD147, TMPRSS2, and NRP1 have been identified in brain cells and may be involved in facilitating SARS-CoV-2 entry into the CNS. Moreover, proteins like P2X7 and Panx-1 may contribute to the pathogenesis of COVID-19. Additionally, the role of the immune system in the gravity of COVID-19 has been investigated with respect to both innate and adaptive immune responses caused by SARS-CoV-2 infection, which can lead to a cytokine storm, tissue damage, and neurological manifestations. A redox imbalance has also been linked to the pathogenesis of COVID-19, potentially causing mitochondrial dysfunction, and generating proinflammatory cytokines. This review summarizes different mechanisms of reactive oxygen species and neuro-inflammation that may contribute to the development of severe COVID-19, and recent progress in the study of immunological events and redox imbalance in neurological complications of COVID-19, and the role of bioinformatics in the study of neurological implications of COVID-19.
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Affiliation(s)
- Abhimanyu Thakur
- Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation-CAS Limited, Hong Kong SAR, Hong Kong.
| | - Vartika Sharma
- Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Sera Averbek
- GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany
- Technische Universität Darmstadt, Darmstadt, Germany
| | - Lifan Liang
- University of Pittsburgh, Pittsburgh, PA, USA
| | - Nirali Pandya
- Department of Chemistry, Faculty of Sciences, National University of Singapore, Singapore, Singapore
| | - Gaurav Kumar
- School of Biosciences and Biomedical Engineering, Department of Clinical Research, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Alma Cili
- Clinic of Hematology, University of Medicine, University Hospital center "Mother Teresa", Tirane, Albania
| | - Kui Zhang
- State Key Laboratory of Resource Insects, College of Sericulture, Textile and Biomass sciences, Southwest University, Chongqing, China.
- Cancer Centre, Medical Research Institute, Southwest University, Chongqing, China.
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Horváth-Szalai Z, Jakabfi-Csepregi R, Szirmay B, Ragán D, Simon G, Kovács-Ábrahám Z, Szabó P, Sipos D, Péterfalvi Á, Miseta A, Csontos C, Kőszegi T, Tóth I. Serum Total Antioxidant Capacity (TAC) and TAC/Lymphocyte Ratio as Promising Predictive Markers in COVID-19. Int J Mol Sci 2023; 24:12935. [PMID: 37629114 PMCID: PMC10454395 DOI: 10.3390/ijms241612935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 08/16/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
SARS-CoV-2 infection might cause a critical disease, and patients' follow-up is based on multiple parameters. Oxidative stress is one of the key factors in the pathogenesis of COVID-19 suggesting that its level could be a prognostic marker. Therefore, we elucidated the predictive value of the serum non-enzymatic total antioxidant capacity (TAC) and that of the newly introduced TAC/lymphocyte ratio in COVID-19. We included 61 COVID-19 (n = 27 ward, n = 34 intensive care unit, ICU) patients and 29 controls in our study. Serum TAC on admission was measured by an enhanced chemiluminescence (ECL) microplate assay previously validated by our research group. TAC levels were higher (p < 0.01) in ICU (median: 407.88 µmol/L) than in ward patients (315.44 µmol/L) and controls (296.60 µmol/L). Besides the classical parameters, both the TAC/lymphocyte ratio and TAC had significant predictive values regarding the severity (AUC-ROC for the TAC/lymphocyte ratio: 0.811; for TAC: 0.728) and acute kidney injury (AUC-ROC for the TAC/lymphocyte ratio: 0.747; for TAC: 0.733) in COVID-19. Moreover, the TAC/lymphocyte ratio had significant predictive value regarding mortality (AUC-ROC: 0.752). Serum TAC and the TAC/lymphocyte ratio might offer valuable information regarding the severity of COVID-19. TAC measured by our ECL microplate assay serves as a promising marker for the prediction of systemic inflammatory diseases.
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Affiliation(s)
- Zoltán Horváth-Szalai
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (R.J.-C.); (B.S.); (D.R.); (Á.P.); (A.M.)
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
| | - Rita Jakabfi-Csepregi
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (R.J.-C.); (B.S.); (D.R.); (Á.P.); (A.M.)
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
| | - Balázs Szirmay
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (R.J.-C.); (B.S.); (D.R.); (Á.P.); (A.M.)
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
| | - Dániel Ragán
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (R.J.-C.); (B.S.); (D.R.); (Á.P.); (A.M.)
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
| | - Gerda Simon
- Department of Anaesthesiology and Intensive Therapy, Medical School, University of Pécs, 7624 Pécs, Hungary; (G.S.); (Z.K.-Á.); (P.S.); (C.C.); (I.T.)
| | - Zoltán Kovács-Ábrahám
- Department of Anaesthesiology and Intensive Therapy, Medical School, University of Pécs, 7624 Pécs, Hungary; (G.S.); (Z.K.-Á.); (P.S.); (C.C.); (I.T.)
| | - Péter Szabó
- Department of Anaesthesiology and Intensive Therapy, Medical School, University of Pécs, 7624 Pécs, Hungary; (G.S.); (Z.K.-Á.); (P.S.); (C.C.); (I.T.)
| | - Dávid Sipos
- 1st Department of Medicine, Division of Infectious Diseases, Medical School, University of Pécs, 7624 Pécs, Hungary;
| | - Ágnes Péterfalvi
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (R.J.-C.); (B.S.); (D.R.); (Á.P.); (A.M.)
| | - Attila Miseta
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (R.J.-C.); (B.S.); (D.R.); (Á.P.); (A.M.)
| | - Csaba Csontos
- Department of Anaesthesiology and Intensive Therapy, Medical School, University of Pécs, 7624 Pécs, Hungary; (G.S.); (Z.K.-Á.); (P.S.); (C.C.); (I.T.)
| | - Tamás Kőszegi
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (R.J.-C.); (B.S.); (D.R.); (Á.P.); (A.M.)
- János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
| | - Ildikó Tóth
- Department of Anaesthesiology and Intensive Therapy, Medical School, University of Pécs, 7624 Pécs, Hungary; (G.S.); (Z.K.-Á.); (P.S.); (C.C.); (I.T.)
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Wang YX, Xu SF, Wang YW, Jiang YX, Qin QW, Wei SN. Curcumin Alleviates Singapore Grouper Iridovirus-Induced Intestine Injury in Orange-Spotted Grouper ( Epinephelus coioides). Antioxidants (Basel) 2023; 12:1584. [PMID: 37627579 PMCID: PMC10452002 DOI: 10.3390/antiox12081584] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/01/2023] [Accepted: 08/05/2023] [Indexed: 08/27/2023] Open
Abstract
Singapore grouper iridovirus (SGIV) is a new ranavirus species in the Iridoviridae family, whose high lethality and rapid spread have resulted in enormous economic losses for the aquaculture industry. Curcumin, a polyphenolic compound, has been proven to possess multiple biological activities, including antibacterial, antioxidant, and antiviral properties. This study was conducted to determine whether curcumin protected orange-spotted grouper (Epinephelus coioides) from SGIV-induced intestinal damage by affecting the inflammatory response, cell apoptosis, oxidative stress, and intestinal microbiota. Random distribution of healthy orange-spotted groupers (8.0 ± 1.0 cm and 9.0 ± 1.0 g) into six experimental groups (each group with 90 groupers): Control, DMSO, curcumin, SGIV, DMSO + SGIV, and curcumin + SGIV. The fish administered gavage received DMSO dilution solution or 640 mg/L curcumin every day for 15 days and then were injected intraperitoneally with SGIV 24 h after the last gavage. When more than half of the groupers in the SGIV group perished, samples from each group were collected for intestinal health evaluation. Our results showed that curcumin significantly alleviated intestine damage and repaired intestinal barrier dysfunction, which was identified by decreased intestine permeability and serum diamine oxidase (DAO) activity and increased expressions of tight junction proteins during SGIV infection. Moreover, curcumin treatment suppressed intestinal cells apoptosis and inflammatory response caused by SGIV and protected intestinal cells from oxidative injury by enhancing the activity of antioxidant enzymes, which was related to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Moreover, we found that curcumin treatment restored the disruption of the intestinal microbiota caused by SGIV infection. Our study provided a theoretical basis for the functional development of curcumin in aquaculture by highlighting the protective effect of curcumin against SGIV-induced intestinal injury.
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Affiliation(s)
- Yue-Xuan Wang
- College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China; (Y.-X.W.); (S.-F.X.); (Y.-W.W.); (Y.-X.J.)
| | - Sui-Feng Xu
- College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China; (Y.-X.W.); (S.-F.X.); (Y.-W.W.); (Y.-X.J.)
| | - Ye-Wen Wang
- College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China; (Y.-X.W.); (S.-F.X.); (Y.-W.W.); (Y.-X.J.)
| | - Yun-Xiang Jiang
- College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China; (Y.-X.W.); (S.-F.X.); (Y.-W.W.); (Y.-X.J.)
| | - Qi-Wei Qin
- College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China; (Y.-X.W.); (S.-F.X.); (Y.-W.W.); (Y.-X.J.)
- Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 528478, China
- Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266000, China
| | - Shi-Na Wei
- College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China; (Y.-X.W.); (S.-F.X.); (Y.-W.W.); (Y.-X.J.)
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Martín Giménez VM, Modrego J, Gómez-Garre D, Manucha W, de las Heras N. Gut Microbiota Dysbiosis in COVID-19: Modulation and Approaches for Prevention and Therapy. Int J Mol Sci 2023; 24:12249. [PMID: 37569625 PMCID: PMC10419057 DOI: 10.3390/ijms241512249] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 07/28/2023] [Accepted: 07/29/2023] [Indexed: 08/13/2023] Open
Abstract
Inflammation and oxidative stress are critical underlying mechanisms associated with COVID-19 that contribute to the complications and clinical deterioration of patients. Additionally, COVID-19 has the potential to alter the composition of patients' gut microbiota, characterized by a decreased abundance of bacteria with probiotic effects. Interestingly, certain strains of these bacteria produce metabolites that can target the S protein of other coronaviruses, thereby preventing their transmission and harmful effects. At the same time, the presence of gut dysbiosis can exacerbate inflammation and oxidative stress, creating a vicious cycle that perpetuates the disease. Furthermore, it is widely recognized that the gut microbiota can metabolize various foods and drugs, producing by-products that may have either beneficial or detrimental effects. In this regard, a decrease in short-chain fatty acid (SCFA), such as acetate, propionate, and butyrate, can influence the overall inflammatory and oxidative state, affecting the prevention, treatment, or worsening of COVID-19. This review aims to explore the current evidence regarding gut dysbiosis in patients with COVID-19, its association with inflammation and oxidative stress, the molecular mechanisms involved, and the potential of gut microbiota modulation in preventing and treating SARS-CoV-2 infection. Given that gut microbiota has demonstrated high adaptability, exploring ways and strategies to maintain good intestinal health, as well as an appropriate diversity and composition of the gut microbiome, becomes crucial in the battle against COVID-19.
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Affiliation(s)
- Virna Margarita Martín Giménez
- Instituto de Investigaciones en Ciencias Químicas, Facultad de Ciencias Químicas y Tecnológicas, Universidad Católica de Cuyo, San Juan 5400, Argentina;
| | - Javier Modrego
- Laboratorio de Riesgo Cardiovascular y Microbiota, Hospital Clínico San Carlos-Instituto de Investigación Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain;
- Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Dulcenombre Gómez-Garre
- Laboratorio de Riesgo Cardiovascular y Microbiota, Hospital Clínico San Carlos-Instituto de Investigación Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain;
- Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Departamento de Fisiología, Facultad de Medicina, Plaza Ramón y Cajal, s/n. Universidad Complutense, 28040 Madrid, Spain
| | - Walter Manucha
- Área de Farmacología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina;
- Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Mendoza 5500, Argentina
| | - Natalia de las Heras
- Departamento de Fisiología, Facultad de Medicina, Plaza Ramón y Cajal, s/n. Universidad Complutense, 28040 Madrid, Spain
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Brecht P, Dring JC, Yanez F, Styczeń A, Mertowska P, Mertowski S, Grywalska E. How Do Minerals, Vitamins, and Intestinal Microbiota Affect the Development and Progression of Heart Disease in Adult and Pediatric Patients? Nutrients 2023; 15:3264. [PMID: 37513682 PMCID: PMC10384570 DOI: 10.3390/nu15143264] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/21/2023] [Accepted: 07/22/2023] [Indexed: 07/30/2023] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death worldwide, far ahead of cancer. Epidemiological data emphasize the participation of many risk factors that increase the incidence of CVDs, including genetic factors, age, and sex, but also lifestyle, mainly nutritional irregularities and, connected with them, overweight and obesity, as well as metabolic diseases. Despite the importance of cardiovascular problems in the whole society, the principles of prevention of CVDs are not widely disseminated, especially among the youngest. As a result, nutritional neglect, growing from childhood and adolescence, translates into the occurrence of numerous disease entities, including CVDs, in adult life. This review aimed to draw attention to the role of selected minerals and vitamins in health and the development and progression of CVDs in adults and children. Particular attention was paid to the effects of deficiency and toxicity of the analyzed compounds in the context of the cardiovascular system and to the role of intestinal microorganisms, which by interacting with nutrients, may contribute to the development of cardiovascular disorders. We hope this article will draw the attention of society and the medical community to emphasize promoting healthy eating and proper eating habits in children and adults, translating into increased awareness and a reduced risk of CVD.
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Affiliation(s)
- Peet Brecht
- Department of Cardiology, Medical University of Lublin, Jaczewskiego 8, 20-093 Lublin, Poland
| | - James Curtis Dring
- Department of Cardiology, Medical University of Lublin, Jaczewskiego 8, 20-093 Lublin, Poland
| | - Felipe Yanez
- Department of Cardiology, Medical University of Lublin, Jaczewskiego 8, 20-093 Lublin, Poland
| | - Agnieszka Styczeń
- Department of Cardiology, Medical University of Lublin, Jaczewskiego 8, 20-093 Lublin, Poland
| | - Paulina Mertowska
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Sebastian Mertowski
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Ewelina Grywalska
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
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47
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Ambrosino A, Chianese A, Zannella C, Piccolella S, Pacifico S, Giugliano R, Franci G, De Natale A, Pollio A, Pinto G, De Filippis A, Galdiero M. Galdieria sulphuraria: An Extremophilic Alga as a Source of Antiviral Bioactive Compounds. Mar Drugs 2023; 21:383. [PMID: 37504915 PMCID: PMC10381441 DOI: 10.3390/md21070383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 06/24/2023] [Accepted: 06/26/2023] [Indexed: 07/29/2023] Open
Abstract
In the last decades, the interest in bioactive compounds derived from natural sources including bacteria, fungi, plants, and algae has significantly increased. It is well-known that aquatic or terrestrial organisms can produce, in special conditions, secondary metabolites with a wide range of biological properties, such as anticancer, antioxidant, anti-inflammatory, and antimicrobial activities. In this study, we focused on the extremophilic microalga Galdieria sulphuraria as a possible producer of bioactive compounds with antiviral activity. The algal culture was subjected to organic extraction with acetone. The cytotoxicity effect of the extract was evaluated by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The antiviral activity was assessed through a plaque assay against herpesviruses and coronaviruses as enveloped viruses and poliovirus as a naked one. The monolayer was treated with different concentrations of extract, ranging from 1 µg/mL to 200 µg/mL, and infected with viruses. The algal extract displayed strong antiviral activity at non-toxic concentrations against all tested enveloped viruses, in particular in the virus pre-treatment against HSV-2 and HCoV-229E, with IC50 values of 1.7 µg/mL and IC90 of 1.8 µg/mL, respectively. However, no activity against the non-enveloped poliovirus has been detected. The inhibitory effect of the algal extract was confirmed by the quantitative RT-PCR of viral genes. Preliminary chemical profiling of the extract was performed using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS), revealing the enrichment in primary fatty acid amides (PFAA), such as oleamide, palmitamide, and pheophorbide A. These promising results pave the way for the further purification of the mixture to explore its potential role as an antiviral agent.
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Affiliation(s)
- Annalisa Ambrosino
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Annalisa Chianese
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Carla Zannella
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Simona Piccolella
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy
| | - Severina Pacifico
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy
| | - Rosa Giugliano
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Gianluigi Franci
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy
| | - Antonino De Natale
- Department of Biology, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
| | - Antonino Pollio
- Department of Biology, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
| | - Gabriele Pinto
- Department of Biology, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
| | - Anna De Filippis
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Massimiliano Galdiero
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
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48
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Qu Y, Haas de Mello A, Morris DR, Jones-Hall YL, Ivanciuc T, Sattler RA, Paessler S, Menachery VD, Garofalo RP, Casola A. SARS-CoV-2 Inhibits NRF2-Mediated Antioxidant Responses in Airway Epithelial Cells and in the Lung of a Murine Model of Infection. Microbiol Spectr 2023; 11:e0037823. [PMID: 37022178 PMCID: PMC10269779 DOI: 10.1128/spectrum.00378-23] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 03/16/2023] [Indexed: 04/07/2023] Open
Abstract
Several viruses have been shown to modulate the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), the master regulator of redox homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, also seems to disrupt the balance between oxidants and antioxidants, which likely contributes to lung damage. Using in vitro and in vivo models of infection, we investigated how SARS-CoV-2 modulates the transcription factor NRF2 and its dependent genes, as well as the role of NRF2 during SARS-CoV-2 infection. We found that SARS-CoV-2 infection downregulates NRF2 protein levels and NRF2-dependent gene expression in human airway epithelial cells and in lungs of BALB/c mice. Reductions in cellular levels of NRF2 seem to be independent of proteasomal degradation and the interferon/promyelocytic leukemia (IFN/PML) pathway. Furthermore, lack of the Nrf2 gene in SARS-CoV-2-infected mice exacerbates clinical disease, increases lung inflammation, and is associated with a trend toward increased lung viral titers, indicating that NRF2 has a protective role during this viral infection. In summary, our results suggest that SARS-CoV-2 infection alters the cellular redox balance by downregulating NRF2 and its dependent genes, which exacerbates lung inflammation and disease, therefore, suggesting that the activation of NRF2 could be explored as therapeutic approach during SARS-CoV-2 infection. IMPORTANCE The antioxidant defense system plays a major function in protecting the organism against oxidative damage caused by free radicals. COVID-19 patients often present with biochemical characteristics of uncontrolled pro-oxidative responses in the respiratory tract. We show herein that SARS-CoV-2 variants, including Omicron, are potent inhibitors of cellular and lung nuclear factor erythroid 2-related factor 2 (NRF2), the master transcription factor that controls the expression of antioxidant and cytoprotective enzymes. Moreover, we show that mice lacking the Nrf2 gene show increased clinical signs of disease and lung pathology when infected with a mouse-adapted strain of SARS-CoV-2. Overall, this study provides a mechanistic explanation for the observed unbalanced pro-oxidative response in SARS-CoV-2 infections and suggests that therapeutic strategies for COVID-19 may consider the use of pharmacologic agents that are known to boost the expression levels of cellular NRF2.
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Affiliation(s)
- Yue Qu
- Department of Pediatrics, The University of Texas Medical Branch, Galveston, Texas, USA
| | - Aline Haas de Mello
- Department of Pediatrics, The University of Texas Medical Branch, Galveston, Texas, USA
| | - Dorothea R. Morris
- Department of Pediatrics, The University of Texas Medical Branch, Galveston, Texas, USA
- Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA
| | - Yava L. Jones-Hall
- School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
| | - Teodora Ivanciuc
- Department of Pediatrics, The University of Texas Medical Branch, Galveston, Texas, USA
| | - Rachel A. Sattler
- Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA
| | - Slobodan Paessler
- Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA
| | - Vineet D. Menachery
- Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA
| | - Roberto P. Garofalo
- Department of Pediatrics, The University of Texas Medical Branch, Galveston, Texas, USA
- Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA
| | - Antonella Casola
- Department of Pediatrics, The University of Texas Medical Branch, Galveston, Texas, USA
- Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA
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49
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Tolmacheva AS, Onvumere MK, Sedykh SE, Timofeeva AM, Nevinsky GA. Catalase Activity of IgGs of Patients Infected with SARS-CoV-2. Int J Mol Sci 2023; 24:10081. [PMID: 37373231 DOI: 10.3390/ijms241210081] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/06/2023] [Accepted: 06/10/2023] [Indexed: 06/29/2023] Open
Abstract
Coronavirus disease (COVID-19), caused by the SARS-CoV-2 coronavirus, leads to various manifestations of the post-COVID syndrome, including diabetes, heart and kidney disease, thrombosis, neurological and autoimmune diseases and, therefore, remains, so far, a significant public health problem. In addition, SARS-CoV-2 infection can lead to the hyperproduction of reactive oxygen species (ROS), causing adverse effects on oxygen transfer efficiency, iron homeostasis, and erythrocytes deformation, contributing to thrombus formation. In this work, the relative catalase activity of the serum IgGs of patients recovered from COVID-19, healthy volunteers vaccinated with Sputnik V, vaccinated with Sputnik V after recovering from COVID-19, and conditionally healthy donors were analyzed for the first time. Previous reports show that along with canonical antioxidant enzymes, the antibodies of mammals with superoxide dismutase, peroxidase, and catalase activities are involved in controlling reactive oxygen species levels. We here show that the IgGs from patients who recovered from COVID-19 had the highest catalase activity, and this was statistically significantly higher each compared to the healthy donors (1.9-fold), healthy volunteers vaccinated with Sputnik V (1.4-fold), and patients vaccinated after recovering from COVID-19 (2.1-fold). These data indicate that COVID-19 infection may stimulate the production of antibodies that degrade hydrogen peroxide, which is harmful at elevated concentrations.
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Affiliation(s)
- Anna S Tolmacheva
- Institute of Chemical Biology and Fundamental Medicine, SB of the RAS, 630090 Novosibirsk, Russia
| | - Margarita K Onvumere
- Institute of Chemical Biology and Fundamental Medicine, SB of the RAS, 630090 Novosibirsk, Russia
| | - Sergey E Sedykh
- Institute of Chemical Biology and Fundamental Medicine, SB of the RAS, 630090 Novosibirsk, Russia
| | - Anna M Timofeeva
- Institute of Chemical Biology and Fundamental Medicine, SB of the RAS, 630090 Novosibirsk, Russia
| | - Georgy A Nevinsky
- Institute of Chemical Biology and Fundamental Medicine, SB of the RAS, 630090 Novosibirsk, Russia
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50
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Zmudzinski M, Rut W, Olech K, Granda J, Giurg M, Burda-Grabowska M, Kaleta R, Zgarbova M, Kasprzyk R, Zhang L, Sun X, Lv Z, Nayak D, Kesik-Brodacka M, Olsen SK, Weber J, Hilgenfeld R, Jemielity J, Drag M. Ebselen derivatives inhibit SARS-CoV-2 replication by inhibition of its essential proteins: PL pro and M pro proteases, and nsp14 guanine N7-methyltransferase. Sci Rep 2023; 13:9161. [PMID: 37280236 DOI: 10.1038/s41598-023-35907-w] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 05/25/2023] [Indexed: 06/08/2023] Open
Abstract
Proteases encoded by SARS-CoV-2 constitute a promising target for new therapies against COVID-19. SARS-CoV-2 main protease (Mpro, 3CLpro) and papain-like protease (PLpro) are responsible for viral polyprotein cleavage-a process crucial for viral survival and replication. Recently it was shown that 2-phenylbenzisoselenazol-3(2H)-one (ebselen), an organoselenium anti-inflammatory small-molecule drug, is a potent, covalent inhibitor of both the proteases and its potency was evaluated in enzymatic and antiviral assays. In this study, we screened a collection of 34 ebselen and ebselen diselenide derivatives for SARS-CoV-2 PLpro and Mpro inhibitors. Our studies revealed that ebselen derivatives are potent inhibitors of both the proteases. We identified three PLpro and four Mpro inhibitors superior to ebselen. Independently, ebselen was shown to inhibit the N7-methyltransferase activity of SARS-CoV-2 nsp14 protein involved in viral RNA cap modification. Hence, selected compounds were also evaluated as nsp14 inhibitors. In the second part of our work, we employed 11 ebselen analogues-bis(2-carbamoylaryl)phenyl diselenides-in biological assays to evaluate their anti-SARS-CoV-2 activity in Vero E6 cells. We present their antiviral and cytoprotective activity and also low cytotoxicity. Our work shows that ebselen, its derivatives, and diselenide analogues constitute a promising platform for development of new antivirals targeting the SARS-CoV-2 virus.
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Affiliation(s)
- Mikolaj Zmudzinski
- Department of Chemical Biology and Bioimaging, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370, Wroclaw, Poland.
| | - Wioletta Rut
- Department of Chemical Biology and Bioimaging, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370, Wroclaw, Poland
| | - Kamila Olech
- Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370, Wroclaw, Poland
| | - Jarosław Granda
- Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370, Wroclaw, Poland
| | - Mirosław Giurg
- Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370, Wroclaw, Poland
| | - Małgorzata Burda-Grabowska
- Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370, Wroclaw, Poland
| | - Rafał Kaleta
- Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370, Wroclaw, Poland
| | - Michala Zgarbova
- Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo Nám. 2, 16610, Prague, Czech Republic
| | - Renata Kasprzyk
- Centre of New Technologies, University of Warsaw, Banacha 2C, 02-097, Warsaw, Poland
- College of Inter-Faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, Banacha 2C, 02-097, Warsaw, Poland
| | - Linlin Zhang
- Institute of Molecular Medicine, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany
| | - Xinyuanyuan Sun
- Institute of Molecular Medicine, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany
| | - Zongyang Lv
- Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA
| | - Digant Nayak
- Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA
| | | | - Shaun K Olsen
- Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA
| | - Jan Weber
- Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo Nám. 2, 16610, Prague, Czech Republic
| | - Rolf Hilgenfeld
- Institute of Molecular Medicine, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, University of Lübeck, 23562, Lübeck, Germany
| | - Jacek Jemielity
- Centre of New Technologies, University of Warsaw, Banacha 2C, 02-097, Warsaw, Poland
| | - Marcin Drag
- Department of Chemical Biology and Bioimaging, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370, Wroclaw, Poland.
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