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Santos PA, Uczay M, Pflüger P, Lobo LAC, Rott MB, Fontenla JA, Rodrigues Siqueira I, Pereira P. Toxicological assessment of the Achyrocline satureioides aqueous extract in the Caenorhabditis elegans alternative model. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2024; 87:730-751. [PMID: 38904345 DOI: 10.1080/15287394.2024.2368618] [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: 06/22/2024]
Abstract
Achyrocline satureioides, popularly called "marcela" in Brazil, is used in traditional medicine in South America. A. satureioides, inflorescences are used for many conditions, including to minimize the Sars-Cov-2 symptoms. Therefore, the aim of this study was to determine the toxicity profile of A. satureioides aqueous extract (ASAE), using the Caenorhabditis elegans (C. elegans) alternative model. Survival, reproduction, development, and transgenerational assays were performed. The effects of ASAE were investigated under conditions of thermal stress and presence of oxidant hydrogen peroxide (H2O2). In addition, C. elegans strains containing high antioxidant enzyme levels and elevated lineages of daf-16, skn-1 and daf-2 regulatory pathways were examined. The ASAE LC50 value was found to be 77.3 ± 4 mg/ml. The concentration of ASAE 10 mg/ml (frequently used in humans) did not exhibit a significant reduction in worm survival at either the L1 or L4 stage, after 24 or 72 hr treatment. ASAE did not markedly alter the body area. In N2 strain, ASAE (10 or 25 mg/ml) reversed the damage initiated by H2O2. In addition, ASAE protected the damage produced by H2O2 in strains containing significant levels of sod-3, gst-4 and ctl - 1,2,3, suggesting modulation in these antioxidant systems by this plant extract. ASAE exposure activated daf-16 and skn-1 stress response transcriptional pathways independently of daf-2, even under extreme stress. Data suggest that ASAE, at the concentrations tested in C. elegans, exhibits a reliable toxicity profile, which may contribute to consideration for safe use in humans.
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Affiliation(s)
- Péterson Alves Santos
- Postgraduate Program in Pharmacology and Therapeutics, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Mariana Uczay
- Postgraduate Program in Pharmacology and Therapeutics, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Pricila Pflüger
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Larissa Aline Carneiro Lobo
- Postgraduate Program in Pharmacology and Therapeutics, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Marilise Brittes Rott
- Department of Microbiology, Immunology and Parasitology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Jose Angel Fontenla
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Ionara Rodrigues Siqueira
- Postgraduate Program in Pharmacology and Therapeutics, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Patrícia Pereira
- Postgraduate Program in Pharmacology and Therapeutics, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
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Kim M, Nowakowska A, Kim J, Kim YB. Anti-Influenza A Potential of Tagetes erecta Linn. Extract Based on Bioinformatics Analysis and In Vitro Assays. Int J Mol Sci 2024; 25:7065. [PMID: 39000173 PMCID: PMC11241564 DOI: 10.3390/ijms25137065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 06/14/2024] [Accepted: 06/19/2024] [Indexed: 07/16/2024] Open
Abstract
Tagetes erecta Linn. (TE) is traditionally used to treat cardiovascular, renal, and gastrointestinal diseases. In this study, we investigated the active compounds and targets of TE extract that may exert antiviral effects against influenza A. Active compounds and targets of TE extract were identified using the Traditional Chinese Medicine Systems Pharmacology database (TCSMP). The influenza A-related gene set was screened using GeneCards and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction (PPI) network was built to establish the hub targets. Pathway and target studies were conducted using Gene Expression Omnibus (GEO). The interactions between active compounds and potential targets were assessed by molecular docking. An in vitro study was performed using antiviral and plaque reduction assays. From the compound and target search, we identified 6 active compounds and 95 potential targets. We retrieved 887 influenza-associated target genes and determined 14 intersecting core targets between TE and influenza. After constructing a compound-target network, we discovered lutein and beta-carotene to be the key compounds. Next, PPI network analysis identified the top three hub genes associated with influenza (IL-6, HIF1A, and IL-1β). Similarly, GEO analysis revealed IL-6, TGFB1, and CXCL8 to be the top three target genes. In our docking study, we identified that lutein and IL-6 had the strongest bindings. Our in vitro experimental results revealed that the TE extract exhibited therapeutic rather than prophylactic effects on influenza disease. We identified lutein as a main active compound in TE extract, and IL-6 as an important target associated with influenza, by using data mining and bioinformatics. Our in vitro findings indicated that TE extract exerted protective properties against the influenza A virus. We speculated that lutein, as a key active component in TE extract, is largely responsible for its antiviral effects. Therefore, we suggest TE extract as an alternative in the treatment of influenza.
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Affiliation(s)
| | | | | | - Young Bong Kim
- Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea; (M.K.); (A.N.); (J.K.)
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Vaiss DP, Rodrigues JL, Yurgel VC, do Carmo Guedes F, da Matta LLM, Barros PAB, Vaz GR, Dos Santos RN, Matte BF, Kupski L, Garda-Buffon J, Bidone J, Muccillo-Baisch AL, Sonvico F, Dora CL. Curcumin and quercetin co-encapsulated in nanoemulsions for nasal administration: A promising therapeutic and prophylactic treatment for viral respiratory infections. Eur J Pharm Sci 2024; 197:106766. [PMID: 38615970 DOI: 10.1016/j.ejps.2024.106766] [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: 12/11/2023] [Revised: 03/19/2024] [Accepted: 04/12/2024] [Indexed: 04/16/2024]
Abstract
One of the most frequent causes of respiratory infections are viruses. Viruses reaching the airways can be absorbed by the human body through the respiratory mucosa and mainly infect lung cells. Several viral infections are not yet curable, such as coronavirus-2 (SARS-CoV-2). Furthermore, the side effect of synthetic antiviral drugs and reduced efficacy against resistant variants have reinforced the search for alternative and effective treatment options, such as plant-derived antiviral molecules. Curcumin (CUR) and quercetin (QUE) are two natural compounds that have been widely studied for their health benefits, such as antiviral and anti-inflammatory activity. However, poor oral bioavailability limits the clinical applications of these natural compounds. In this work, nanoemulsions (NE) co-encapsulating CUR and QUE designed for nasal administration were developed as promising prophylactic and therapeutic treatments for viral respiratory infections. The NEs were prepared by high-pressure homogenization combined with the phase inversion temperature technique and evaluated for their physical and chemical characteristics. In vitro assays were performed to evaluate the nanoemulsion retention into the porcine nasal mucosa. In addition, the CUR and QUE-loaded NE antiviral activity was tested against a murine β-COV, namely MHV-3. The results evidenced that CUR and QUE loaded NE had a particle size of 400 nm and retention in the porcine nasal mucosa. The antiviral activity of the NEs showed a percentage of inhibition of around 99 %, indicating that the developed NEs has interesting properties as a therapeutic and prophylactic treatment against viral respiratory infections.
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Affiliation(s)
- Daniela Pastorim Vaiss
- Postgraduate Program in Health Sciences, Federal University of Rio Grande, Rio Grande 96203-900, Brazil
| | - Jamile Lima Rodrigues
- Graduate Program in Food Science and Engineering, Federal University of Rio Grande, Rio Grande 96203-900 Brazil, RS, Brazil
| | - Virginia Campello Yurgel
- Postgraduate Program in Health Sciences, Federal University of Rio Grande, Rio Grande 96203-900, Brazil
| | - Frank do Carmo Guedes
- Postgraduate Program in Health Sciences, Federal University of Rio Grande, Rio Grande 96203-900, Brazil
| | | | | | - Gustavo Richter Vaz
- Postgraduate Program in Health Sciences, Federal University of Rio Grande, Rio Grande 96203-900, Brazil
| | - Raíssa Nunes Dos Santos
- Virology Laboratory of the Biotechnology Startup Núcleo Vitro, Porto Alegre 91040-600, Brazil; Laboratory of Bioinformatics and Biotechnology, Campus de Gurupi, Federal University of Tocantins, Gurupi 77402-970, Brazil
| | - Bibiana Franzen Matte
- Virology Laboratory of the Biotechnology Startup Núcleo Vitro, Porto Alegre 91040-600, Brazil
| | - Larine Kupski
- Laboratory for Mycotoxins and Food Science, School of Chemistry and Food, Federal University of Rio Grande - FURG, Italy Avenue 8 km, Campus Carreiros, 96203-900 Rio Grande, RS, Brazil
| | - Jaqueline Garda-Buffon
- Laboratory for Mycotoxins and Food Science, School of Chemistry and Food, Federal University of Rio Grande - FURG, Italy Avenue 8 km, Campus Carreiros, 96203-900 Rio Grande, RS, Brazil
| | - Juliana Bidone
- Center of Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas, Campus Capão do Leão, 96010-610 Pelotas, RS, Brazil
| | - Ana Luiza Muccillo-Baisch
- Postgraduate Program in Health Sciences, Federal University of Rio Grande, Rio Grande 96203-900, Brazil
| | - Fabio Sonvico
- Food and Drug Department, University of Parma, Parma, Italy.
| | - Cristiana Lima Dora
- Postgraduate Program in Health Sciences, Federal University of Rio Grande, Rio Grande 96203-900, Brazil.
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Li Y, Huo S, Yin Z, Tian Z, Huang F, Liu P, Liu Y, Yu F. Retracted and republished from: "The current state of research on influenza antiviral drug development: drugs in clinical trial and licensed drugs". mBio 2024; 15:e0017524. [PMID: 38551343 PMCID: PMC11077966 DOI: 10.1128/mbio.00175-24] [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: 05/09/2024] Open
Abstract
Influenza viruses (IVs) threaten global human health due to the high morbidity, infection, and mortality rates. Currently, the influenza drugs recommended by the Food and Drug Administration are oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These recommended antivirals are currently effective for major subtypes of IVs as the compounds target conserved domains in neuraminidase or polymerase acidic (PA) protein. However, this trend may gradually change due to the selection of antiviral drugs and the natural evolution of IVs. Therefore, there is an urgent need to develop drugs related to the treatment of influenza to deal with the next pandemic. Here, we summarized the cutting-edge research in mechanism of action, inhibitory activity, and clinical efficacy of drugs that have been approved and drugs that are still in clinical trials for influenza treatment. We hope this review will provide up-to-date and comprehensive information on influenza antivirals and generate hypotheses for screens and development of new broad-spectrum influenza drugs in the near future.
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Affiliation(s)
- Yanbai Li
- Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, Hebei Wild Animal Health Center, College of Life Sciences, Hebei Agricultural University, Baoding, China
| | - Shanshan Huo
- Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, Hebei Wild Animal Health Center, College of Life Sciences, Hebei Agricultural University, Baoding, China
| | - Zhe Yin
- Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, Hebei Wild Animal Health Center, College of Life Sciences, Hebei Agricultural University, Baoding, China
| | - Zuguang Tian
- Department of High-Tech Development, Baoding City Science and Technology Bureau, Baoding, China
| | - Fang Huang
- Epidemic Prevention Laboratory, Tongzhou District Center For Animal Disease Control and Prevention, Beijing, China
| | - Peng Liu
- Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, Hebei Wild Animal Health Center, College of Life Sciences, Hebei Agricultural University, Baoding, China
| | - Yue Liu
- Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA
| | - Fei Yu
- Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, Hebei Wild Animal Health Center, College of Life Sciences, Hebei Agricultural University, Baoding, China
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Macedo C, Costa PC, Rodrigues F. Bioactive compounds from Actinidia arguta fruit as a new strategy to fight glioblastoma. Food Res Int 2024; 175:113770. [PMID: 38129059 DOI: 10.1016/j.foodres.2023.113770] [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: 08/03/2023] [Revised: 11/10/2023] [Accepted: 11/22/2023] [Indexed: 12/23/2023]
Abstract
In recent years, there has been a significant demand for natural products as a mean of disease prevention or as an alternative to conventional medications. The driving force for this change is the growing recognition of the abundant presence of valuable bioactive compounds in natural products. On recent years Actinia arguta fruit, also known as kiwiberry, has attracted a lot of attention from scientific community due to its richness in bioactive compounds, including phenolic compounds, organic acids, vitamins, carotenoids and fiber. These bioactive compounds contribute to the fruit's diverse outstanding biological activities such as antioxidant, anti-inflammatory, neuroprotective, immunomodulatory, and anti-cancer properties. Due to these properties, the fruit may have the potential to be used in the treatment/prevention of various types of cancer, including glioblastoma. Glioblastoma is the most aggressive form of brain cancer, displaying 90 % of recurrence rate within a span of 2 years. Despite the employment of an aggressive approach, the prognosis remains unfavorable, emphasizing the urgent requirement for the development of new effective treatments. The preclinical evidence suggests that kiwiberry has potential impact on glioblastoma by reducing the cancer self-renewal, modulating the signaling pathways involved in the regulation of the cell phenotype and metabolism, and influencing the consolidation of the tumor microenvironment. Even though, challenges such as the imprecise composition and concentration of bioactive compounds, and its low bioavailability after oral administration may be drawbacks to the development of kiwiberry-based treatments, being urgent to ensure the safety and efficacy of kiwiberry for the prevention and treatment of glioblastoma. This review aims to highlight the potential impact of A. arguta bioactive compounds on glioblastoma, providing novel insights into their applicability as complementary or alternative therapies.
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Affiliation(s)
- Catarina Macedo
- REQUIMTE/LAQV, ISEP, Polytechnic of Porto, Rua Dr. António Bernardino de Almeida, 4249-015 Porto, Portugal; REQUIMTE/UCIBIO, MedTech-Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
| | - Paulo C Costa
- REQUIMTE/UCIBIO, MedTech-Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
| | - Francisca Rodrigues
- REQUIMTE/LAQV, ISEP, Polytechnic of Porto, Rua Dr. António Bernardino de Almeida, 4249-015 Porto, Portugal.
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Mohammadi S, Moghadam MD, Nasiriasl M, Akhzari M, Barazesh M. Insights into the Therapeutic and Pharmacological Properties of Resveratrol as a Nutraceutical Antioxidant Polyphenol in Health Promotion and Disease Prevention. Curr Rev Clin Exp Pharmacol 2024; 19:327-354. [PMID: 38192151 DOI: 10.2174/0127724328268507231218051058] [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: 06/22/2023] [Revised: 11/20/2023] [Accepted: 11/22/2023] [Indexed: 01/10/2024]
Abstract
Resveratrol (3, 5, 4'-trihydroxystilbene) is a polyphenolic derivative with herbal origin. It has attracted considerable attention in recent decades. Many studies have revealed the benefits of Resveratrol over several human disease models, including heart and neurological diseases, nephroprotective, immune regulation, antidiabetic, anti-obesity, age-related diseases, antiviral, and anticancer in experimental and clinical conditions. Recently, the antioxidant and anti-inflammatory activities of Resveratrol have been observed, and it has been shown that Resveratrol reduces inflammatory biomarkers, such as tissue degradation factor, cyclooxygenase 2, nitric oxide synthase, and interleukins. All of these activities appear to be dependent on its structural properties, such as the number and position of the hydroxyl group, which regulates oxidative stress, cell death, and inflammation. Resveratrol is well tolerated and safe even at higher pharmacological doses and desirably affects cardiovascular, neurological, and diabetic diseases. Consequently, it is plausible that Resveratrol can be regarded as a beneficial nutritional additive and a complementary drug, particularly for therapeutic applications. The present review provides an overview of currently available investigations on preventive and therapeutic characteristics and the main molecular mechanisms of Resveratrol and its potent derivatives in various diseases. Thus, this review would enhance knowledge and information about Resveratrol and encourage researchers worldwide to consider it as a pharmaceutical drug to struggle with future health crises against different human disorders.
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Affiliation(s)
- Shiva Mohammadi
- Department of Medical Biotechnology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Maryam Dalaei Moghadam
- Razi Herbal Medicines Research Center, Department of Endodontic, Faculty of Dentistry, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Maryam Nasiriasl
- Radiology Department, Fasa University of Medical Sciences, Fasa, Iran
| | - Morteza Akhzari
- School of Nursing, Larestan University of Medical Sciences, Larestan, Iran
| | - Mahdi Barazesh
- School of Paramedical Sciences, Gerash University of Medical Sciences, Gerash, Iran
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Bastos CIM, Dani C, Cechinel LR, da Silva Neves AH, Rasia FB, Bianchi SE, da Silveira Loss E, Lamers ML, Meirelles G, Bassani VL, Siqueira IR. Achyrocline satureioides as an adjuvant therapy for the management of mild viral respiratory infections in the context of COVID-19: Preliminary results of a randomized, placebo-controlled, and open-label clinical trial. Phytother Res 2023; 37:5354-5365. [PMID: 37583121 DOI: 10.1002/ptr.7976] [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: 02/26/2022] [Revised: 06/02/2023] [Accepted: 07/23/2023] [Indexed: 08/17/2023]
Abstract
We evaluated the impact of an Achyrocline satureioides inflorescence infusion on the clinical outcomes of viral respiratory infections, including those caused by SARS-CoV-2, in a monocentric, randomized, open-label, placebo-controlled clinical trial. Patients with symptoms of viral respiratory infection, including suspected cases of COVID-19, were included and assigned to receive either A. satureioides (n = 57) or Malus domestica (n = 67) infusions twice a day for 14 days. All participants were included before the RT-PCR results, performed using a nasopharyngeal swab. The patients were further divided into subgroups according to real-time polymerase chain reaction results: SARS-CoV-2-positive and SARS-CoV-2-negative subgroups for statistical analyses. We assessed clinical outcomes, such as the latency to resolution of cough, dyspnea, fever, sore throat, chest pain, smell and taste dysfunctions, diarrhea, nausea, abdominal pain, and loss of appetite; hospitalization; and mortality with questionnaires and medical records. The subjects that received early A. satureioides infusion showed a significant reduction in the average number of days with respiratory and neurological symptoms compared with the control group (M. domestica infusion). We conclude that A. satureioides is a safe agent and, in combination with standard care, improves viral respiratory infection symptoms, especially those related to COVID-19.
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Affiliation(s)
- Catherina Isdra Moszkowicz Bastos
- Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Caroline Dani
- Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Laura Reck Cechinel
- Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Arthur Hipolito da Silva Neves
- Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Fabiana Briato Rasia
- Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Sara Elis Bianchi
- Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Eloisa da Silveira Loss
- Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Marcelo Lazzaron Lamers
- Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Gabriela Meirelles
- Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Valquiria Linck Bassani
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Ionara Rodrigues Siqueira
- Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
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Li Y, Huo S, Yin Z, Tian Z, Huang F, Liu P, Liu Y, Yu F. The current state of research on influenza antiviral drug development: drugs in clinical trial and licensed drugs. mBio 2023; 14:e0127323. [PMID: 37610204 PMCID: PMC10653855 DOI: 10.1128/mbio.01273-23] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/24/2023] Open
Abstract
Influenza viruses (IVs) threaten global human health due to the high morbidity, infection, and mortality rates. Currently, the influenza drugs recommended by the FDA are oseltamivir, zanamivir, peramivir, and baloxavir marboxil. Notably, owing to the high variability of IVs, no drug exists that can effectively treat all types and subtypes of IVs. Moreover, the current trend of drug resistance is likely to continue as the viral genome is constantly mutating. Therefore, there is an urgent need to develop drugs related to the treatment of influenza to deal with the next pandemic. Here, we summarized the cutting-edge research in mechanism of action, inhibitory activity, and clinical efficacy of drugs that have been approved and drugs that are still in clinical trials for influenza treatment. We hope this review will provide up-to-date and comprehensive information on influenza antivirals and generate hypotheses for screens and development of new broad-spectrum influenza drugs in the near future.
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Affiliation(s)
- Yanbai Li
- Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, Hebei Wild Animal Health Center, College of Life Sciences, Hebei Agricultural University, Baoding, China
| | - Shanshan Huo
- Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, Hebei Wild Animal Health Center, College of Life Sciences, Hebei Agricultural University, Baoding, China
| | - Zhe Yin
- Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, Hebei Wild Animal Health Center, College of Life Sciences, Hebei Agricultural University, Baoding, China
| | - Zuguang Tian
- Baoding City Science and Technology Bureau, Baoding, China
| | - Fang Huang
- Tongzhou District Center For Animal Disease Control and Prevention, Beijing, China
| | - Peng Liu
- Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, Hebei Wild Animal Health Center, College of Life Sciences, Hebei Agricultural University, Baoding, China
| | - Yue Liu
- Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA
| | - Fei Yu
- Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, Hebei Wild Animal Health Center, College of Life Sciences, Hebei Agricultural University, Baoding, China
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Cherian S, Hacisayidli KM, Kurian R, Mathews A. Therapeutically important bioactive compounds of the genus Polygonum L. and their possible interventions in clinical medicine. J Pharm Pharmacol 2023; 75:301-327. [PMID: 36757388 DOI: 10.1093/jpp/rgac105] [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: 06/28/2022] [Accepted: 12/26/2022] [Indexed: 02/10/2023]
Abstract
OBJECTIVES Increasing literature data have suggested that the genus Polygonum L. possesses pharmacologically important plant secondary metabolites. These bioactive compounds are implicated as effective agents in preclinical and clinical practice due to their pharmacological effects such as anti-inflammatory, anticancer, antidiabetic, antiaging, neuroprotective or immunomodulatory properties among many others. However, elaborate pharmacological and clinical data concerning the bioavailability, tissue distribution pattern, dosage and pharmacokinetic profiles of these compounds are still scanty. KEY FINDINGS The major bioactive compounds implicated in the therapeutic effects of Polygonum genus include phenolic and flavonoid compounds, anthraquinones and stilbenes, such as quercetin, resveratrol, polydatin and others, and could serve as potential drug leads or as adjuvant agents. Data from in-silico network pharmacology and computational molecular docking studies are also highly helpful in identifying the possible drug target of pathogens or host cell machinery. SUMMARY We provide an up-to-date overview of the data from pharmacodynamic, pharmacokinetic profiles and preclinical (in-vitro and in-vivo) investigations and the available clinical data on some of the therapeutically important compounds of genus Polygonum L. and their medical interventions, including combating the outbreak of the COVID-19 pandemic.
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Affiliation(s)
- Sam Cherian
- Indian Society for Plant Physiology, New Delhi, India
| | - Kushvar Mammadova Hacisayidli
- Department of Hygiene and Food Safety, Veterinary Medicine Faculty, Azerbaijan State Agricultural University, Ganja City, Azerbaijan
| | - Renju Kurian
- Department of Pathology, Manipal University College, Melaka, Malaysia
| | - Allan Mathews
- Faculty of Pharmacy, Quest International University Perak, Ipoh, Malaysia
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Volobueva AС, Zarubaev V, Fedorchenko T, Lipunova G, Tungusov V, Chupakhin O. Antiviral properties of verdazyls and leucoverdazyls and their activity against group B enteroviruses. RUSSIAN JOURNAL OF INFECTION AND IMMUNITY 2023. [DOI: 10.15789/2220-7619-val-2065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/09/2023]
Abstract
Introduction: Enteroviruses are non-enveloped viruses of the Enterovirus genus of the Picornaviridae family. They cause human diseases ranging from respiratory diseases to more severe cases, including polio, encephalitis, myocarditis, and pancreatitis. To date, there are no approved direct-acting antiviral drugs for the treatment of enterovirus diseases, therefore search for new small molecules - inhibitors of the enterovirus life cycle is important.
Objective: to characterize the antiviral properties of new stable free radicals, verdazyls, and their precursors, leucoverdazyls. Leucoverdazyls have previously been shown to have antioxidant potential.
Materials and methods: leucoverdazyls and verdazyls were synthesized in the Laboratory of coordination compounds, Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, Ekaterinburg, Russian Federation. The following strains and cell cultures were used: influenza A virus (strain A/Puerto Rico/8/1934 H1N1), Coxsackie virus B3 (CVB3, Nancy strain), Coxsackie virus B4 (CVB4, Powers strain), Coxsackie virus B5, herpes simplex virus type 1 (HSV1) and human adenovirus 5 (Ad5) obtained from the collection of the Pasteur Research Institute (St. Petersburg). The following cell cultures were used: MDCK (ATCC #CCL-34), Vero (ATCC #CCL-81), A549 (ATCC #CCL-185). Infectious activity of viruses was assessed by end point titration. The cytoprotective activity and cytotoxicity of the compounds were evaluated using MTT test. The antiviral activity of the compounds was evaluated in the viral yield reduction assay. The virucidal activity of the compounds was evaluated after incubation of the compounds in a cell-free system with Coxsackie B4 virus for 1 hour. To investigate the mechanism of action of the leader compound, a time-of-addition assay was performed.
Results:
Leucoverdazyls, unlike verdazyls, have cytoprotective activity when a permissive culture is infected with the Coxsackie B3 virus. The leading compound was identified: 1a, which demonstrated a high inhibitory ability against a wide panel of influenza B enteroviruses in micromolar range (IC50=5.48 M and 0.72 M for Coxsackie B3 and Coxsackie B4, respectively) and its activity was superior to pleconaril (IC50=15.2 and IC50=1.91). Nevertheless, pleconaril acted as a more powerful inhibitor than 1a towards Coxsackievirus B5. The compound showed only slight activity against influenza A (RNA virus), no activity against Ad5 and HSV1 (DNA viruses). 1a have no virucidal activity. The maximum decrease in the titers of viral progeny with the addition of 1a was observed in the early and middle stages of the life cycle of the Coxsackie virus.
Conclusion:
Leucoverdazyls are potent inhibitors of group B enteroviruses in vitro. Leucoverdazyl 1a doesnt belong to capsid binder class of inhibitors and has no virucidal activity against coxsackievirus. Further studies are needed to elucidate their precise mechanisms of action including assessment of its direct impact on intracellular ROS generation, resistant clone selection and mapping of resistance mutations. We plan to expand the library of leucoverdazyls through targeted chemical modifications in order to disclose its pharmacophore and improve their virus-inhibiting properties. Nevertheless, the results of the study can serve as a basis for future development of novel antivirals to use in monotherapy or in combinational treatment of enteroviral infections.
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11
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Kwon EB, Li W, Kim YS, Kim B, Chung HS, Go Y, Ko HJ, Song JH, Kim YH, Choi CW, Choi JG. Vitisin B inhibits influenza A virus replication by multi-targeting neuraminidase and virus-induced oxidative stress. Acta Pharm Sin B 2023; 13:174-191. [PMID: 36815046 PMCID: PMC9939323 DOI: 10.1016/j.apsb.2022.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/25/2022] [Accepted: 06/16/2022] [Indexed: 11/17/2022] Open
Abstract
The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.
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Affiliation(s)
- Eun-Bin Kwon
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea
| | - Wei Li
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea
| | - Young Soo Kim
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea
| | - Buyun Kim
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea
| | - Hwan-Suck Chung
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea
| | - Younghoon Go
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea
| | - Hyun-Jeong Ko
- Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea
| | - Jae-Hyoung Song
- Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea
| | - Young Ho Kim
- College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
- Corresponding authors. Tel./Fax.: +82 42 8215933/+82 42 8236566, +82 31 8886131/+82 31 8886139, +82 53 9403866/+82 53 9403899
| | - Chun Whan Choi
- Natural Product Research Team, Biocenter, Gyeonggido Business and Science Accelerator, Gyeonggi-Do 16229, Republic of Korea
- Corresponding authors. Tel./Fax.: +82 42 8215933/+82 42 8236566, +82 31 8886131/+82 31 8886139, +82 53 9403866/+82 53 9403899
| | - Jang-Gi Choi
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea
- Corresponding authors. Tel./Fax.: +82 42 8215933/+82 42 8236566, +82 31 8886131/+82 31 8886139, +82 53 9403866/+82 53 9403899
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12
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Raghav A, Giri R, Agarwal S, Kala S, Jeong GB. Protective role of engineered extracellular vesicles loaded quercetin nanoparticles as anti-viral therapy against SARS-CoV-2 infection: A prospective review. Front Immunol 2022; 13:1040027. [PMID: 36569877 PMCID: PMC9773252 DOI: 10.3389/fimmu.2022.1040027] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 11/23/2022] [Indexed: 12/13/2022] Open
Abstract
Quercetin (QCT) is a naturally occurring phenolic flavonoid compound with inbuilt characteristics of antioxidant, anti-inflammatory, and immune protection. Several recent studies have shown that QCT and QCTits nanoparticles have therapeutic potential against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Novel therapeutics also include the implication of extracellular vesicles (EVs) to protect from SARS-CoV-2 viral infection. This article highlighted the therapeutic/prophylactic potential of engineered EVs loaded with QCT against SARS-CoV-2 infection. Several biotechnological engineering approaches are available to deliver EVs loaded with QCT nanoparticles. Among these biotechnological advances, a specific approach with significantly higher efficiency and yield has to be opted to fabricate such drug delivery of nano molecules, especially to combat SARS-CoV-2 infection. The current treatment regime protects the human body from virus infection but has some limitations including drugs and long-term steroid side effects. However, the vaccine strategy is somehow effective in inhibiting the spread of coronavirus disease-19 (COVID-19) infection. Moreover, the proposed exosomal therapy met the current need to repair the damaged tissue along with inhibition of COVID-19-associated complications at the tissue level. These scientific findings expand the possibilities and predictability of developing a novel and cost-effective therapeutic approach that combines the dual molecule, EVs and QCT nanoparticles, to treat SARS-CoV-2 infection. Therefore, the most suitable engineering method to fabricate such a drug delivery system should be better understood before developing novel therapeutics for clinical purposes.
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Affiliation(s)
- Alok Raghav
- Department of Anatomy and Cell Biology, College of Medicine, Gachon University, Incheon, South Korea,Multidisciplinary Research Unit, GSVM Medical College, Kanpur, Uttar Pradesh, India
| | - Richa Giri
- Kailashpat Singhania (KPS), Institute of Medicine, GSVM Medical College, Kanpur, Uttar Pradesh, India
| | - Saurabh Agarwal
- Kailashpat Singhania (KPS), Institute of Medicine, GSVM Medical College, Kanpur, Uttar Pradesh, India
| | - Sanjay Kala
- Department of Surgery, GSVM Medical College, Kanpur, Uttar Pradesh, India
| | - Goo-Bo- Jeong
- Department of Anatomy and Cell Biology, College of Medicine, Gachon University, Incheon, South Korea,*Correspondence: Goo-Bo- Jeong,
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13
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Bouazzaoui W, Xiao P, Couve‐Bonnaire S, Bouillon J, Mulengi JK. Chronic Inflammation and Chronic Diseases: Potential Healing with Glutathione‐Inspired Fragments. ChemistrySelect 2022. [DOI: 10.1002/slct.202203051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Wafaa Bouazzaoui
- Laboratory of Organic Chemistry Natural Products and Analysis University of Tlemcen P.O. BOX 117 Tlemcen 13 000 Algeria
| | - Pan Xiao
- Normandie Université COBRA, UMR 6014 et FR 3038 INSA Rouen, CNRS Université de Rouen 1, Rue Tesnière 76821 Mont Saint-Aignan Cedex France
| | - Samuel Couve‐Bonnaire
- Normandie Université COBRA, UMR 6014 et FR 3038 INSA Rouen, CNRS Université de Rouen 1, Rue Tesnière 76821 Mont Saint-Aignan Cedex France
| | - Jean‐Philippe Bouillon
- Normandie Université COBRA, UMR 6014 et FR 3038 INSA Rouen, CNRS Université de Rouen 1, Rue Tesnière 76821 Mont Saint-Aignan Cedex France
| | - Joseph Kajima Mulengi
- Department of Chemistry Faculty of Sciences Faculty of Sciences University of Tlemcen P.O. Box 119 13000 Tlemcen Algeria
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14
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Potential Roles of Anti-Inflammatory Plant-Derived Bioactive Compounds Targeting Inflammation in Microvascular Complications of Diabetes. Molecules 2022; 27:molecules27217352. [PMID: 36364178 PMCID: PMC9657994 DOI: 10.3390/molecules27217352] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 10/25/2022] [Accepted: 10/26/2022] [Indexed: 12/15/2022] Open
Abstract
Diabetes mellitus (DM) is a group of metabolic disorders, the characteristics of which include chronic hyperglycemia owing to defects in insulin function, insulin secretion, or both. Inflammation plays a crucial role in DM pathogenesis and innate immunity in the development of microvascular complications of diabetes. In addition, hyperglycemia and DM mediate a proinflammatory microenvironment that can result in various microvascular complications, including diabetic nephropathy (DNP), diabetic neuropathy (DN), and diabetic retinopathy (DR). DNP is a major cause of end-stage renal disease. DNP can lead to albuminuria, decreased filtration, mesangium expansion, thickening of the basement membrane, and eventually renal failure. Furthermore, inflammatory cells can accumulate in the interstitium and glomeruli to deteriorate DNP. DN is another most prevalent microvascular complication of DM and the main cause of high mortality, disability, and a poor quality of life. DNs have a wide range of clinical manifestations because of the types of fiber dysfunctions and complex structures of the peripheral nervous system. DR is also a microvascular and multifactorial disease, as well as a major cause of visual impairment globally. Pathogenesis of DR is yet to be fully revealed, however, numerous studies have already confirmed the role of inflammation in the onset and advancement of DR. Despite evidence, and better knowledge regarding the pathogenesis of these microvascular complications of diabetes, there is still a deficiency of effective therapies. Bioactive compounds are mainly derived from plants, and these molecules have promising therapeutic potential. In this review, evidence and molecular mechanisms regarding the role of inflammation in various microvascular complications of diabetes including DNP, DN, and DR, have been summarized. The therapeutic potential of several bioactive compounds derived from plants in the treatment of these microvascular complications of diabetes has also been discussed.
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15
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Juneja D, Gupta A, Kataria S, Singh O. Role of high dose vitamin C in management of hospitalised COVID-19 patients: A minireview. World J Virol 2022; 11:300-309. [PMID: 36188745 PMCID: PMC9523318 DOI: 10.5501/wjv.v11.i5.300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/22/2022] [Accepted: 08/31/2022] [Indexed: 02/05/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the most dreadful viruses the mankind has witnessed. It has caused world-wide havoc and wrecked human life. In our quest to find therapeutic options to counter this threat, several drugs have been tried, with varying success. Certain agents like corticosteroids, some anti-virals and immunosuppressive drugs have been found useful in improving clinical outcomes. Vitamin C, a water-soluble vitamin with good safety profile, has been tried to reduce progression and im-prove outcomes of patients with coronavirus disease 2019 (COVID-19). Because of its anti-oxidant and immunomodulatory properties, the role of vitamin C has expanded well beyond the management of scurvy and it is increasingly been employed in the treatment of critically ill patients with sepsis, septic shock, acute pancreatitis and even cancer. However, in spite of many case series, observational studies and even randomised control trials, the role of vitamin C remains ambiguous. In this review, we will be discussing the scientific rationale and the current clinical evidence for using high dose vitamin C in the management of COVID-19 patients.
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Affiliation(s)
- Deven Juneja
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
| | - Anish Gupta
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
| | - Sahil Kataria
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
| | - Omender Singh
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
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16
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Lee J, Kim KS, Na K. Intranasal administration of an aronia extract and carrageenan nanocomposite for the prevention of influenza A H1N1 virus infection. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2022. [DOI: 10.1007/s40005-022-00591-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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17
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Shanmugavadivu A, Balagangadharan K, Selvamurugan N. Angiogenic and Osteogenic Effects of Flavonoids in Bone Regeneration. Biotechnol Bioeng 2022; 119:2313-2330. [PMID: 35718883 DOI: 10.1002/bit.28162] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 06/14/2022] [Indexed: 11/10/2022]
Abstract
Bone is a highly vascularised tissue that relies on a close spatial and temporal interaction between blood vessels and bone cells. As a result, angiogenesis is critical for bone formation and healing. The vascular system supports bone regeneration by delivering oxygen, nutrients, and growth factors, as well as facilitating efficient cell-cell contact. Most clinical applications of engineered bone grafts are hampered by insufficient vascularization after implantation. Over the last decade, a number of flavonoids have been reported to have osteogenic-angiogenic potential in bone regeneration because of their excellent bioactivity, low cost, availability, and minimal in vivo toxicity. During new bone formation, the osteoinductive nature of certain flavonoids is involved in regulating multiple signaling pathways contributing toward the osteogenic-angiogenic coupling. This review briefly outlines the osteogenic-angiogenic potential of those flavonoids and the mechanisms of their action in promoting bone regeneration. However, further studies are needed to investigate their delivery strategies and establish their clinical efficacy. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Abinaya Shanmugavadivu
- Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, 603 203, Tamil Nadu, India
| | - K Balagangadharan
- Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, 603 203, Tamil Nadu, India
| | - N Selvamurugan
- Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, 603 203, Tamil Nadu, India
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18
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Khan A, Iqtadar S, Mumtaz SU, Heinrich M, Pascual-Figal DA, Livingstone S, Abaidullah S. Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19—Results From a Pilot Open-Label, Randomized Controlled Trial. Front Pharmacol 2022; 13:898062. [PMID: 35747751 PMCID: PMC9211374 DOI: 10.3389/fphar.2022.898062] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 04/27/2022] [Indexed: 12/15/2022] Open
Abstract
Background: Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant activities. Objective: The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical University, Lahore, Pakistan. Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic COVID-19 outpatients were randomized to receive either the standard of care (SOC) (n = 25) (control arm) or a daily oral co-supplementation of 168 mg curcumin, 260 mg quercetin, and 9 µg (360 IU) of cholecalciferol, as two oral soft capsules b.i.d. as an add-on to the SOC (n = 25) (CQC arm) for 14 days. The SOC includes paracetamol with or without antibiotic (azithromycin). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, and complete blood count were evaluated at baseline and follow-up day seven. Results: Patients who received the CQC adjuvant therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. five (20.0%) of the control arm, p = 0.009. COVID-19- associated acute symptoms were rapidly resolved in the CQC arm, i.e., 15 (60.0%) vs. 10 (40.0%) of the control arm, p = 0.154. Patients in the CQC arm experienced a greater fall in serum CRP levels, i.e., from (median (IQR) 34.0 (21.0, 45.0) to 11.0 (5.0, 16.0) mg/dl as compared to the control arm, i.e., from 36.0 (28.0, 47.0) to 22.0 (15.0, 25.0) mg/dl, p = 0.006. The adjuvant therapy of co-supplementation of CQC was safe and well-tolerated by all 25 patients and no treatment-emergent effects, complications, side effects, or serious adverse events were reported. Conclusion: The co-supplementation of CQC may possibly have a therapeutic role in the early stage of COVID-19 infection including speedy negativization of the SARS-CoV-2 RT-PCR test, resolution of acute symptoms, and modulation of the hyperinflammatory response. In combination with routine care, the adjuvant co-supplementation of CQC may possibly help in the speedy recovery from early-stage mild to moderate symptoms of COVID-19. Further research is warranted. Clinical Trial Registration:Clinicaltrials.gov, identifier NCT05130671
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Affiliation(s)
- Amjad Khan
- INEOS Oxford Institute for AMR Research, University of Oxford, Oxford, United Kingdom
- Department of Biochemistry, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan
- *Correspondence: Amjad Khan,
| | - Somia Iqtadar
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Sami Ullah Mumtaz
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Michael Heinrich
- UCL School of Pharmacy, University of London, London, United Kingdom
| | - Domingo A. Pascual-Figal
- Department of Cardiology, University of Murcia Hospital Universitario Virgen de la Arrixaca Murcia, Murcia, Spain
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | | | - Sajid Abaidullah
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
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19
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Hernández-Ochoa B, Ortega-Cuellar D, González-Valdez A, Cárdenas-Rodríguez N, Mendoza-Torreblanca JG, Contreras-García IJ, Pichardo-Macías LA, Bandala C, Gómez-Manzo S. COVID-19 in G6PD-deficient patients, oxidative stress, and neuropathology. Curr Top Med Chem 2022; 22:1307-1325. [PMID: 35578850 DOI: 10.2174/1568026622666220516111122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 03/01/2022] [Accepted: 03/12/2022] [Indexed: 11/22/2022]
Abstract
Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that regulates energy metabolism mainly through the pentose phosphate pathway (PPP). It is well known that this enzyme participates in the antioxidant/oxidant balance via the synthesis of energy-rich molecules: nicotinamide adenine dinucleotide phosphate reduced (NADPH), the reduced form of flavin adenine dinucleotide (FADH) and glutathione (GSH), controlling reactive oxygen species generation. Coronavirus disease 19 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered a public health problem which has caused approximately 4.5 million deaths since December 2019. In relation to the role of G6PD in COVID-19 development, it is known from the existing literature that G6PD-deficient patients infected with SARS-CoV-2 are more susceptible to thrombosis and hemolysis, suggesting that G6PD deficiency facilitates infection by SARS-CoV-2. In relation to G6PD and neuropathology, it has been observed that deficiency of this enzyme is also present with an increase in oxidative markers. In relation to the role of G6PD and the neurological manifestations of COVID-19, it has been reported that the enzymatic deficiency in patients infected with SARS-CoV-2 exacerbates the disease, and, in some clinical reports, an increase in hemolysis and thrombosis was observed when patients were treated with hydroxychloroquine (OH-CQ), a drug with oxidative properties. In the present work, we summarize the evidence of the role of G6PD in COVID-19 and its possible role in the generation of oxidative stress and glucose metabolism deficits and inflammation present in this respiratory disease and its progression including neurological manifestations.
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Affiliation(s)
- Beatriz Hernández-Ochoa
- Laboratorio de Inmunoquímica, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City, 06720, Mexico
| | - Daniel Ortega-Cuellar
- Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
| | - Abigail González-Valdez
- Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
| | - Noemí Cárdenas-Rodríguez
- Laboratorio de Neurociencias, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
| | | | | | - Luz Adriana Pichardo-Macías
- Departamento de Fisiología, Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Mexico City, 07738, Mexico
| | - Cindy Bandala
- Division de Neurociencias, Instituto Nacional de Rehabilitación, Secretaría de Salud, Mexico City, 14389, Mexico.,Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, 11340, Mexico
| | - Saúl Gómez-Manzo
- Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
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Lin HY, Zeng YT, Lin CJ, Harroun SG, Anand A, Chang L, Wu CJ, Lin HJ, Huang CC. Partial carbonization of quercetin boosts the antiviral activity against H1N1 influenza A virus. J Colloid Interface Sci 2022; 622:481-493. [PMID: 35525149 DOI: 10.1016/j.jcis.2022.04.124] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 04/19/2022] [Accepted: 04/21/2022] [Indexed: 11/19/2022]
Abstract
Inflenza A viruses (IAVs) are highly transmissible and pathogenic Orthomyxoviruses, which have led to worldwide outbreaks and seasonal pandemics of acute respiratory diseases, causing serious threats to public health. Currently used anti-influenza drugs may cause neurological side effects, and they are increasingly less effective against mutant strains. To help prevent the spread of IAVs, in this work, we have developed quercetin-derived carbonized nanogels (CNGsQur) that display potent viral inhibitory, antioxidative, and anti-inflammatory activities. The antiviral CNGsQur were synthesized by mild carbonization of quercetin (Qur), which successfully preserved their antioxidative and anti-inflammatory properties while also contributed enhanced properties, such as water solubility, viral binding, and biocompatibility. Antiviral assays of co-treatment, pre-treatment, and post-treatment indicate that CNGsQur interacts with the virion, revealing that the major antiviral mechanism resulting in the inhibition of the virus is by their attachment on the cell surface. Among them, the selectivity index (SI) of CNGsQur270 (>857.1) clearly indicated its great potential for clinical application in IAVs inhibition, which was much higher than that of pristine quercetin (63.7) and other clinical drugs (4-81). Compared with quercetin at the same dose, the combined effects of viral inhibition, antioxidative and anti-inflammatory activities impart the superior therapeutic effects of CNGsQur270 aerosol inhalation in the treatment of IAVs infection, as evidenced by a mouse model. These CNGsQur effectively prevent the spread of IAVs and suppress virus-induced inflammation while also exhibiting good in vivo biocompatibility. CNGsQur shows much promise as a clinical therapeutic agent against infection by IVAs.
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Affiliation(s)
- Hung-Yun Lin
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202301, Taiwan
| | - Yu-Ting Zeng
- Department of Food Science, National Taiwan Ocean University, Keelung 202301, Taiwan
| | - Chin-Jung Lin
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202301, Taiwan
| | - Scott G Harroun
- Department of Chemistry, Université de Montréal, Montréal, Québec H3C 3J7, Canada
| | - Anisha Anand
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202301, Taiwan
| | - Lung Chang
- Department of Pediatrics, Nursing and Management, Mackay Memorial Hospital and Mackay Junior College of Medicine, Taipei 10449, Taiwan
| | - Chang-Jer Wu
- Department of Food Science, National Taiwan Ocean University, Keelung 202301, Taiwan; Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202301, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
| | - Han-Jia Lin
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202301, Taiwan; Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202301, Taiwan
| | - Chih-Ching Huang
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202301, Taiwan; Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202301, Taiwan; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
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21
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Nguyen TLA, Bhattacharya D. Antimicrobial Activity of Quercetin: An Approach to Its Mechanistic Principle. Molecules 2022; 27:molecules27082494. [PMID: 35458691 PMCID: PMC9029217 DOI: 10.3390/molecules27082494] [Citation(s) in RCA: 156] [Impact Index Per Article: 52.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/04/2022] [Accepted: 04/07/2022] [Indexed: 02/04/2023] Open
Abstract
Quercetin, an essential plant flavonoid, possesses a variety of pharmacological activities. Extensive literature investigates its antimicrobial activity and possible mechanism of action. Quercetin has been shown to inhibit the growth of different Gram-positive and Gram-negative bacteria as well as fungi and viruses. The mechanism of its antimicrobial action includes cell membrane damage, change of membrane permeability, inhibition of synthesis of nucleic acids and proteins, reduction of expression of virulence factors, mitochondrial dysfunction, and preventing biofilm formation. Quercetin has also been shown to inhibit the growth of various drug-resistant microorganisms, thereby suggesting its use as a potent antimicrobial agent against drug-resistant strains. Furthermore, certain structural modifications of quercetin have sometimes been shown to enhance its antimicrobial activity compared to that of the parent molecule. In this review, we have summarized the antimicrobial activity of quercetin with a special focus on its mechanistic principle. Therefore, this review will provide further insights into the scientific understanding of quercetin’s mechanism of action, and the implications for its use as a clinically relevant antimicrobial agent.
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22
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van Brummelen R, van Brummelen AC. The potential role of resveratrol as supportive antiviral in treating conditions such as COVID-19 - A formulator's perspective. Biomed Pharmacother 2022; 148:112767. [PMID: 35240527 PMCID: PMC8884665 DOI: 10.1016/j.biopha.2022.112767] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/21/2022] [Accepted: 02/27/2022] [Indexed: 11/18/2022] Open
Abstract
With an increased transmissibility but milder form of disease of the omicron variant of COVID-19 and the newer antivirals often still out of reach of many populations, a refocus of the current treatment regimens is required. Safe, affordable, and available adjuvant treatments should also be considered and known drugs and substances need to be repurposed and tested. Resveratrol, a well-known antioxidant of natural origin, shown to act as an antiviral as well as playing a role in immune stimulation, down regulation of the pro-inflammatory cytokine release and reducing lung injury by reducing oxidative stress, is such an option. New initiatives and collaborations will however need to be found to unleash resveratrol's full potential in the pharmaceutical market.
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23
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Kang H, Hu H, Park SK. Serum antioxidant status and mortality from influenza and pneumonia in US adults. Public Health Nutr 2022; 25:1-10. [PMID: 35000647 PMCID: PMC9271125 DOI: 10.1017/s1368980022000027] [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: 08/17/2021] [Revised: 12/09/2021] [Accepted: 01/04/2022] [Indexed: 11/06/2022]
Abstract
OBJECTIVE We examined the association between serum antioxidant status and mortality from influenza and pneumonia in US adults. DESIGN Serum concentrations of antioxidants included vitamin C, vitamin A, vitamin E, sum of α- and β-carotene, β-cryptoxanthin, lutein + zeaxanthin and lycopene. We computed total antioxidant capacity (TAC) as a measure of composite antioxidant status in serum. Survey-weighted Cox proportional hazard models were used to compute hazard ratios (HR) and 95 % CI comparing quartiles of each antioxidant and TAC. SETTING Data from the US National Health and Nutrition Examination Survey (NHANES)-III. PARTICIPANTS A total of 7428 NHANES-III participants ≥45 years of age. RESULTS With a weighted-median follow-up of 16·8 years, 154 participants died from influenza/pneumonia. After adjustment for covariates, serum vitamin C, the sum of α- and β-carotene and TAC were nonlinearly associated with influenza/pneumonia mortality, with the statistically significant smallest HR at the third quartile v. the first quartile (HR = 0·38 (95 % CI: 0·19, 0·77), 0·29 (0·16, 0·51) and 0·30 (0·15, 0·59), respectively). HR comparing the fourth v. the first quartiles were weaker and nonsignificant: 0·57 (95 % CI: 0·27, 1·17), 0·70 (0·41, 1·19) and 0·65 (0·31, 1·35), respectively. Serum lycopene had a monotonic association with influenza/pneumonia mortality (HR = 0·43 (95 % CI: 0·23, 0·83) comparing the fourth v. the first quartile, Pfor trend = 0·01). CONCLUSIONS The current study suggests that antioxidant intake as reflected by serum concentrations may reduce mortality risk from influenza or pneumonia in the US general population. These findings warrant further confirmation in other populations with different settings (e.g. a shorter-term association with influenza infection).
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Affiliation(s)
- Habyeong Kang
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI48109, USA
| | - Howard Hu
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Sung Kyun Park
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI48109, USA
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
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24
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Mitochondria-mediated oxidative stress during viral infection. Trends Microbiol 2022; 30:679-692. [DOI: 10.1016/j.tim.2021.12.011] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 12/20/2021] [Accepted: 12/21/2021] [Indexed: 12/20/2022]
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25
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Önal H, Arslan B, Üçüncü Ergun N, Topuz Ş, Yilmaz Semerci S, Kurnaz ME, Molu YM, Bozkurt MA, Süner N, Kocataş A. Treatment of COVID-19 patients with quercetin: a prospective, single center, randomized, controlled trial. Turk J Biol 2021; 45:518-529. [PMID: 34803451 PMCID: PMC8573830 DOI: 10.3906/biy-2104-16] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 07/02/2021] [Indexed: 12/15/2022] Open
Abstract
Scientific research continues on new preventive and therapeutic strategies against severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). So far, there is no proven curative treatment, and a valid alternative therapeutic approach needs to be developed. This study is designed to evaluate the effect of quercetin in COVID-19 treatment. This was a single-centre, prospective randomized controlled cohort study. Routine care versus QCB (quercetin, vitamin C, bromelain) supplementation was compared between 429 patients with at least one chronic disease and moderate-to-severe respiratory symptoms. Demographic features, signs, laboratory results and drug administration data of patients were recorded. The endpoint was that QCB supplementation was continued throughout the follow-up period from study baseline to discharge, intubation, or death. The most common complaints at the time of hospital admission were fatigue (62.4%), cough (61.1%), anorexia (57%), thirst (53.7%), respiratory distress (51%) and chills (48.3%). The decrease in CRP and ferritin levels was higher in the QCB group (all Ps were < 0.05). In the QCB group, the increase in platelet and lymphocyte counts was higher (all Ps were < 0.05). QCB did not reduce the risk of events during follow-up. Adjustments for statistically significant parameters, including the lung stage, use of favipiravir and presence of comorbidity did not change the results. While there was no difference between the groups in terms of event frequency, the QCB group had more advanced pulmonary findings. QCB supplement is shown to have a positive effect on laboratory recovery. While there was no difference between the groups in terms of event frequency, QCB supplement group had more advanced pulmonar findings, and QCB supplement is shown to have a positive effect on laboratory recovery/results. Therefore, we conclude that further studies involving different doses and plasma level measurements are required to reveal the dose/response relationship and bioavailability of QCB for a better understanding of the role of QCB in the treatment of SARS CoV-2.
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Affiliation(s)
- Hasan Önal
- Department of Pediatric Nutrition and Metabolism Clinics, İstanbul Kanuni Sultan Süleyman Training and Research Hospital, İstanbul Turkey
| | - Bengü Arslan
- Department of Pediatric Nutrition and Metabolism Clinics, İstanbul Kanuni Sultan Süleyman Training and Research Hospital, İstanbul Turkey
| | - Nurcan Üçüncü Ergun
- Department of Pediatric Nutrition and Metabolism Clinics, İstanbul Kanuni Sultan Süleyman Training and Research Hospital, İstanbul Turkey
| | - Şeyma Topuz
- Department of Pediatric Nutrition and Metabolism Clinics, İstanbul Kanuni Sultan Süleyman Training and Research Hospital, İstanbul Turkey
| | - Seda Yilmaz Semerci
- Department of Neonatology, İstanbul Kanuni Sultan Süleyman Training and Research Hospital, İstanbul Turkey
| | - Mehmet Eren Kurnaz
- Department of Pediatric Nutrition and Metabolism Clinics, İstanbul Kanuni Sultan Süleyman Training and Research Hospital, İstanbul Turkey
| | - Yulet Miray Molu
- Department of Pediatric Nutrition and Metabolism Clinics, İstanbul Kanuni Sultan Süleyman Training and Research Hospital, İstanbul Turkey
| | - Mehmet Abdussamet Bozkurt
- Department of General Surgery, İstanbul Kanuni Sultan Süleyman Training and Research Hospital, İstanbul Turkey
| | - Nurettin Süner
- Department of General Medicine, İstanbul Kanuni Sultan Süleyman Training and Research Hospital, İstanbul Turkey
| | - Ali Kocataş
- Department of General Surgery, İstanbul Kanuni Sultan Süleyman Training and Research Hospital, İstanbul Turkey
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26
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Specific Cytokine Profiles Predict the Severity of Influenza A Pneumonia: A Prospectively Multicenter Pilot Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9533044. [PMID: 34692846 PMCID: PMC8528594 DOI: 10.1155/2021/9533044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 08/30/2021] [Accepted: 10/04/2021] [Indexed: 02/06/2023]
Abstract
Purpose Studying the cytokine profiles in influenza A pneumonia could be helpful to better understand the pathogenesis of the disease and predict its prognosis. Patients and Methods. Patients with influenza A pneumonia (including 2009H1N1, H1N1, H3N1, and H7N1) hospitalized in six hospitals from January 2017 to October 2018 were enrolled (ClinicalTrials.gov ID, NCT03093220). Sputum samples were collected within 24 hours after admission and subsequently analyzed for cytokine profiles using a Luminex assay. Results A total of 35 patients with influenza A pneumonia were included in the study. The levels of IL-6, IFN-γ, and IL-2 were increased in patients with severe influenza A pneumonia (n =10) (P = 0.002, 0.009, and 0.008, respectively), while those of IL-5, IL-25, IL-17A, and IL-22 were decreased compared to patients with nonsevere pneumonia (P = 0.0001, 0.009, 0.0001, and 0.006, respectively). The levels of IL-2 and IL-6 in the nonsurvivors (n = 5) were significantly higher than those in the survivors (P = 0.043 and 0.0001, respectively), while the levels of IL-5, IL-17A, and IL-22 were significantly lower (P = 0.001, 0.012, and 0.043, respectively). The IL-4/IL-17A ratio has the potential to be a good predictor (AUC = 0.94, P < 0.05, sensitivity = 88.89%, specificity = 92.31%) and an independent risk factor (OR, 95% CI: 3.772, 1.188-11.975; P < 0.05) for intermittent positive pressure ventilation (n = 9). Conclusion Significant dysregulation of cytokine profiles can be observed in patients with severe influenza A pneumonia.
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27
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Molina-Montes E, Uzhova I, Verardo V, Artacho R, García-Villanova B, Jesús Guerra-Hernández E, Kapsokefalou M, Malisova O, Vlassopoulos A, Katidi A, Koroušić Seljak B, Modic R, Eftimov T, Hren I, Valenčič E, Šatalić Z, Panjkota Krbavčić I, Vranešić Bender D, Giacalone D, Bom Frøst M, Konic Ristic A, Milesevic J, Nikolic M, Kolay E, Güney M, Kriaucioniene V, Czlapka-Matyasik M, Bykowska-Derda A, Kujundzic E, Taljić I, Brka M, Spiroski I, Cunha Velho S, Patrícia Sousa Pinto S, Nascimento Monteiro I, Adriana Pereira J, Dolores Ruíz-López M, Rodríguez-Pérez C. Impact of COVID-19 confinement on eating behaviours across 16 European countries: The COVIDiet cross-national study. Food Qual Prefer 2021; 93:104231. [PMID: 36569642 PMCID: PMC9759462 DOI: 10.1016/j.foodqual.2021.104231] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 02/08/2021] [Accepted: 03/04/2021] [Indexed: 12/27/2022]
Abstract
We aimed to evaluate the changes in eating behaviours of the adult population across 16 European countries due to the COVID-19 confinement and to evaluate whether these changes were somehow related to the severity of the containment measures applied in each country. An anonymous online self-reported questionnaire on socio-demographic characteristics, validated 14-items Mediterranean diet (MedDiet) Adherence Screener (MEDAS) as a reference of a healthy diet, eating and lifestyle behaviours prior to and during the COVID-19 confinement was used to collect data. The study included an adult population residing in 16 European countries at the time of the survey. Aggregated Stringency Index (SI) score, based on data from the Oxford COVID-19 Government Response Tracker, was calculated for each country at the time the questionnaire was distributed (range: 0-100). A total of 36,185 participants completed the questionnaire (77.6% female, 75.2% with high educational level and 42.7% aged between 21 and 35 years). In comparison to pre-confinement, a significantly higher adherence to the MedDiet during the confinement was observed across all countries (overall MEDAS score prior to- and during confinement: 5.23 ± 2.06 vs. 6.15 ± 2.06; p < 0.001), with the largest increase seen in Greece and North Macedonia. The highest adherence to MedDiet during confinement was found in Spain and Portugal (7.18 ± 1.84 and 7.34 ± 1.95, respectively). Stricter contingency restrictions seemed to lead to a significantly higher increase in the adherence to the MedDiet. The findings from this cross-sectional study could be used to inform current diet-related public health guidelines to ensure optimal nutrition is followed among the population, which in turn would help to alleviate the current public health crisis.
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Affiliation(s)
- Esther Molina-Montes
- Department of Nutrition and Food Science, University of Granada, Campus of Cartuja, 18071 Granada, Spain,Institute of Nutrition and Food Technology (INYTA) ‘José Mataix’, Biomedical Research Centre, University of Granada, Avenida del Conocimiento s/n, E-18071 Granada, Spain,Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain,Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública CIBERESP, Madrid, Spain
| | - Irina Uzhova
- Department of Health and Nutritional Sciences, Institute of Technology Sligo, Ash Ln, Bellanode, Sligo F91 YW50, Ireland
| | - Vito Verardo
- Department of Nutrition and Food Science, University of Granada, Campus of Cartuja, 18071 Granada, Spain,Institute of Nutrition and Food Technology (INYTA) ‘José Mataix’, Biomedical Research Centre, University of Granada, Avenida del Conocimiento s/n, E-18071 Granada, Spain
| | - Reyes Artacho
- Department of Nutrition and Food Science, University of Granada, Campus of Cartuja, 18071 Granada, Spain
| | - Belén García-Villanova
- Department of Nutrition and Food Science, University of Granada, Campus of Cartuja, 18071 Granada, Spain
| | | | - Maria Kapsokefalou
- Department of Food Science and Nutrition, Agricultural University of Athens, Iera Odos 75, Athens 11855, Greece
| | - Olga Malisova
- Department of Food Science and Nutrition, Agricultural University of Athens, Iera Odos 75, Athens 11855, Greece
| | - Antonis Vlassopoulos
- Department of Food Science and Nutrition, Agricultural University of Athens, Iera Odos 75, Athens 11855, Greece
| | - Alexandra Katidi
- Department of Food Science and Nutrition, Agricultural University of Athens, Iera Odos 75, Athens 11855, Greece
| | | | - Robert Modic
- Computer Systems Department, Jožef Stefan Institute, Jamova cesta 39, Ljubljana, Slovenia
| | - Tome Eftimov
- Computer Systems Department, Jožef Stefan Institute, Jamova cesta 39, Ljubljana, Slovenia
| | - Irena Hren
- General Hospital Novo mesto, Šmihelska cesta 1, 8000 Novo mesto, Slovenia
| | - Eva Valenčič
- Computer Systems Department, Jožef Stefan Institute, Jamova cesta 39, Ljubljana, Slovenia
| | - Zvonimir Šatalić
- University of Zagreb, Faculty of Food Technology and Biotechnology, Pierottijeva ul. 6, 10000 Zagreb, Croatia
| | - Ines Panjkota Krbavčić
- University of Zagreb, Faculty of Food Technology and Biotechnology, Pierottijeva ul. 6, 10000 Zagreb, Croatia
| | - Darija Vranešić Bender
- University Hospital Centre Zagreb, Department of Internal Medicine, Division of Gastroenterology and Hepatology & Unit of Clinical Nutrition, Kišpatićeva ul. 12, 10000 Zagreb, Croatia
| | - Davide Giacalone
- Department of Technology and Innovation, University of Southern Denmark, Campusvej 55, DK5230 Odense, Denmark
| | - Michael Bom Frøst
- Department of Food Science, University of Copenhagen, Rolighedsvej 26, DK-1958 Frederiksberg, Denmark
| | - Aleksandra Konic Ristic
- Institute for Medical Research, Centre of Research Excellence in Nutrition and Metabolism, University of Belgrade, National Institute of Serbia, Beograd, Tadeuša Košćuška 1, PAK 104 201, 11158 Belgrade, Serbia,Institute of Food and Health, University College Dublin, Belfield, Dublin 4, Ireland
| | - Jelena Milesevic
- Institute for Medical Research, Centre of Research Excellence in Nutrition and Metabolism, University of Belgrade, National Institute of Serbia, Beograd, Tadeuša Košćuška 1, PAK 104 201, 11158 Belgrade, Serbia
| | - Marina Nikolic
- Institute for Medical Research, Centre of Research Excellence in Nutrition and Metabolism, University of Belgrade, National Institute of Serbia, Beograd, Tadeuša Košćuška 1, PAK 104 201, 11158 Belgrade, Serbia
| | - Ezgi Kolay
- Poznan University of Life Sciences, Department of Human Nutrition and Dietetics, Wojska Polskiego 28, 60-637 Poznan, Poland
| | - Merve Güney
- Bezmialem Vakif University, Medical Faculty Hospital, Nutrition and Diet Department, Vatan Cad. 34093, Istanbul, Turkey
| | - Vilma Kriaucioniene
- Faculty of Public Health, Lithuanian University of Health Sciences, Tilzes str. 18, LT-47181 Kaunas, Lithuania
| | - Magdalena Czlapka-Matyasik
- Poznan University of Life Sciences, Department of Human Nutrition and Dietetics, Wojska Polskiego 28, 60-637 Poznan, Poland
| | - Aleksandra Bykowska-Derda
- Poznan University of Life Sciences, Department of Human Nutrition and Dietetics, Wojska Polskiego 28, 60-637 Poznan, Poland
| | - Enisa Kujundzic
- Center for Health Ecology of Institute of Public Health of Montenegro, Dzona Dzeksona bb, 81 000 Podgorica, Montenegro
| | - Irzada Taljić
- Faculty of Agriculture and Food Sciences, University of Sarajevo, Sarajevo, Bosnia and Herzegovina, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and Herzegovina
| | - Muhamed Brka
- Faculty of Agriculture and Food Sciences, University of Sarajevo, Sarajevo, Bosnia and Herzegovina, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and Herzegovina
| | - Igor Spiroski
- Institute of Public Health, 50. Divizija 6, 1000 Skopje, Macedonia,Faculty of Medicine, Ss. Cyril and Methodius University, 50. Divizija 6, 1000 Skopje, Macedonia
| | | | | | | | | | - María Dolores Ruíz-López
- Department of Nutrition and Food Science, University of Granada, Campus of Cartuja, 18071 Granada, Spain,Institute of Nutrition and Food Technology (INYTA) ‘José Mataix’, Biomedical Research Centre, University of Granada, Avenida del Conocimiento s/n, E-18071 Granada, Spain
| | - Celia Rodríguez-Pérez
- Institute of Nutrition and Food Technology (INYTA) ‘José Mataix’, Biomedical Research Centre, University of Granada, Avenida del Conocimiento s/n, E-18071 Granada, Spain,Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain,Department of Nutrition and Food Science, University of Granada, Campus of Melilla, Calle Santander, 1. 52071, Melilla, Spain,Corresponding author at: Department of Nutrition and Food Science, University of Granada, Campus of Melilla, Calle Santander, 1. 52071, Melilla, Spain
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28
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Teafatiller T, Agrawal S, De Robles G, Rahmatpanah F, Subramanian VS, Agrawal A. Vitamin C Enhances Antiviral Functions of Lung Epithelial Cells. Biomolecules 2021; 11:1148. [PMID: 34439814 PMCID: PMC8394979 DOI: 10.3390/biom11081148] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 07/29/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
Vitamin C is well documented to have antiviral functions; however, there is limited information about its effect on airway epithelial cells-the first cells to encounter infections. Here, we examined the effect of vitamin C on human bronchial epithelium transformed with Ad12-SV40 2B (BEAS-2B) cells, and observed that sodium-dependent vitamin C transporter 2 (SVCT2) was the primary vitamin C transporter. Transcriptomic analysis revealed that treating BEAS-2B cells with vitamin C led to a significant upregulation of several metabolic pathways and interferon-stimulated genes (ISGs) along with a downregulation of pathways involved in lung injury and inflammation. Remarkably, vitamin C also enhanced the expression of the viral-sensing receptors retinoic acid-inducible gene 1 (RIG-1) and melanoma differentiation-associated protein 5 (MDA-5), which was confirmed at the protein and functional levels. In addition, the lungs of l-gulono-γ-lactone oxidase knockout (GULO-KO) mice also displayed a marked decrease in these genes compared to wild-type controls. Collectively, our findings indicate that vitamin C acts at multiple levels to exert its antiviral and protective functions in the lungs.
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Affiliation(s)
- Trevor Teafatiller
- Division of Gastroenterology, Department of Medicine, University of California, Irvine, CA 92697, USA;
| | - Sudhanshu Agrawal
- Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA;
| | - Gabriela De Robles
- Department of Pathology, University of California, Irvine, CA 92697, USA; (G.D.R.); (F.R.)
| | - Farah Rahmatpanah
- Department of Pathology, University of California, Irvine, CA 92697, USA; (G.D.R.); (F.R.)
| | - Veedamali S. Subramanian
- Division of Gastroenterology, Department of Medicine, University of California, Irvine, CA 92697, USA;
| | - Anshu Agrawal
- Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA;
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29
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Milenkovic D, Ruskovska T, Rodriguez-Mateos A, Heiss C. Polyphenols Could Prevent SARS-CoV-2 Infection by Modulating the Expression of miRNAs in the Host Cells. Aging Dis 2021; 12:1169-1182. [PMID: 34341700 PMCID: PMC8279534 DOI: 10.14336/ad.2021.0223] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 02/23/2021] [Indexed: 12/19/2022] Open
Abstract
Coronaviruses (CoVs) are single-stranded RNA viruses which following virus attachment and entry into the host cell, particularly type 2 pneumocytes but also endothelial cells, release RNA into cytosol where it serves as a matrix for the host translation machinery to produce viral proteins. The viral RNA in cytoplasm can interact with host cell microRNAs which can degrade viral RNA and/or prevent viral replication. As such host cellular miRNAs represent key cellular mediators of antiviral defense. Polyphenols, plant food bioactives, exert antiviral properties, which is partially due to their capacity to modulate the expression of miRNAs. The objective of this work was to assess if polyphenols can play a role in prevention of SARS-CoV-2 associated complications by modulating the expression of host miRNAs. To test this hypothesis, we performed literature search to identify miRNAs that could bind SARS-CoV-2 RNA as well as miRNAs which expression can be modulated by polyphenols in lung, type 2 pneumocytes or endothelial cells. We identified over 600 miRNAs that have capacity to bind viral RNA and 125 miRNAs which expression can be modulated by polyphenols in the cells of interest. We identified that there are 17 miRNAs with both the capacity to bind viral RNA and which expression can be modulated by polyphenols. Some of these miRNAs have been identified as having antiviral properties or can target genes involved in regulation of processes of viral replication, apoptosis or viral infection. Taken together this analysis suggests that polyphenols could modulate expression of miRNAs in alveolar and endothelial cells and exert antiviral capacity.
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Affiliation(s)
- Dragan Milenkovic
- Université Clermont Auvergne, INRAE, UNH, F-63000 Clermont-Ferrand, France.
- Department of Internal Medicine, Division of Cardiovascular Medicine, School of Medicine, University of California Davis, Davis, CA 95616, USA.
| | - Tatjana Ruskovska
- Faculty of Medical Sciences, Goce Delcev University, Stip, North Macedonia.
| | | | - Christian Heiss
- Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Science and Medicine, King's College London, London, UK.
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30
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Reynolds D, Huesemann M, Edmundson S, Sims A, Hurst B, Cady S, Beirne N, Freeman J, Berger A, Gao S. Viral inhibitors derived from macroalgae, microalgae, and cyanobacteria: A review of antiviral potential throughout pathogenesis. ALGAL RES 2021; 57:102331. [PMID: 34026476 PMCID: PMC8128986 DOI: 10.1016/j.algal.2021.102331] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/24/2021] [Accepted: 04/27/2021] [Indexed: 12/19/2022]
Abstract
Viruses are abiotic obligate parasites utilizing complex mechanisms to hijack cellular machinery and reproduce, causing multiple harmful effects in the process. Viruses represent a growing global health concern; at the time of writing, COVID-19 has killed at least two million people around the world and devastated global economies. Lingering concern regarding the virus' prevalence yet hampers return to normalcy. While catastrophic in and of itself, COVID-19 further heralds in a new era of human-disease interaction characterized by the emergence of novel viruses from natural sources with heretofore unseen frequency. Due to deforestation, population growth, and climate change, we are encountering more viruses that can infect larger groups of people with greater ease and increasingly severe outcomes. The devastation of COVID-19 and forecasts of future human/disease interactions call for a creative reconsideration of global response to infectious disease. There is an urgent need for accessible, cost-effective antiviral (AV) drugs that can be mass-produced and widely distributed to large populations. Development of AV drugs should be informed by a thorough understanding of viral structure and function as well as human biology. To maximize efficacy, minimize cost, and reduce development of drug-resistance, these drugs would ideally operate through a varied set of mechanisms at multiple stages throughout the course of infection. Due to their abundance and diversity, natural compounds are ideal for such comprehensive therapeutic interventions. Promising sources of such drugs are found throughout nature; especially remarkable are the algae, a polyphyletic grouping of phototrophs that produce diverse bioactive compounds. While not much literature has been published on the subject, studies have shown that these compounds exert antiviral effects at different stages of viral pathogenesis. In this review, we follow the course of viral infection in the human body and evaluate the AV effects of algae-derived compounds at each stage. Specifically, we examine the AV activities of algae-derived compounds at the entry of viruses into the body, transport through the body via the lymph and blood, infection of target cells, and immune response. We discuss what is known about algae-derived compounds that may interfere with the infection pathways of SARS-CoV-2; and review which algae are promising sources for AV agents or AV precursors that, with further investigation, may yield life-saving drugs due to their diversity of mechanisms and exceptional pharmaceutical potential.
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Affiliation(s)
- Daman Reynolds
- Pacific Northwest National Laboratory, Marine and Coastal Research Laboratory, Sequim, WA, USA
| | - Michael Huesemann
- Pacific Northwest National Laboratory, Marine and Coastal Research Laboratory, Sequim, WA, USA
| | - Scott Edmundson
- Pacific Northwest National Laboratory, Marine and Coastal Research Laboratory, Sequim, WA, USA
| | - Amy Sims
- Pacific Northwest National Laboratory, Chemical and Biological Signatures Group, Richland, WA, USA
| | - Brett Hurst
- Institute for Antiviral Research, Utah State University, Logan, UT, USA
| | - Sherry Cady
- Pacific Northwest National Laboratory, Marine and Coastal Research Laboratory, Sequim, WA, USA
| | - Nathan Beirne
- Pacific Northwest National Laboratory, Marine and Coastal Research Laboratory, Sequim, WA, USA
| | - Jacob Freeman
- Pacific Northwest National Laboratory, Marine and Coastal Research Laboratory, Sequim, WA, USA
| | - Adam Berger
- Pacific Northwest National Laboratory, Marine and Coastal Research Laboratory, Sequim, WA, USA
| | - Song Gao
- Pacific Northwest National Laboratory, Marine and Coastal Research Laboratory, Sequim, WA, USA
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Decaffeination and Neuraminidase Inhibitory Activity of Arabica Green Coffee ( Coffea arabica) Beans: Chlorogenic Acid as a Potential Bioactive Compound. Molecules 2021; 26:molecules26113402. [PMID: 34199752 PMCID: PMC8200017 DOI: 10.3390/molecules26113402] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 05/28/2021] [Accepted: 06/02/2021] [Indexed: 11/17/2022] Open
Abstract
Coffee has been studied for its health benefits, including prevention of several chronic diseases, such as type 2 diabetes mellitus, cancer, Parkinson’s, and liver diseases. Chlorogenic acid (CGA), an important component in coffee beans, was shown to possess antiviral activity against viruses. However, the presence of caffeine in coffee beans may also cause insomnia and stomach irritation, and increase heart rate and respiration rate. These unwanted effects may be reduced by decaffeination of green bean Arabica coffee (GBAC) by treatment with dichloromethane, followed by solid-phase extraction using methanol. In this study, the caffeine and chlorogenic acid (CGA) level in the coffee bean from three different areas in West Java, before and after decaffeination, was determined and validated using HPLC. The results showed that the levels of caffeine were reduced significantly, with an order as follows: Tasikmalaya (2.28% to 0.097% (97 ppm), Pangalengan (1.57% to 0.049% (495 ppm), and Garut (1.45% to 0.00002% (0.2 ppm). The CGA levels in the GBAC were also reduced as follows: Tasikmalaya (0.54% to 0.001% (118 ppm), Pangalengan (0.97% to 0.0047% (388 ppm)), and Garut (0.81% to 0.029% (282 ppm). The decaffeinated samples were then subjected to the H5N1 neuraminidase (NA) binding assay to determine its bioactivity as an anti-influenza agent. The results show that samples from Tasikmalaya, Pangalengan, and Garut possess NA inhibitory activity with IC50 of 69.70, 75.23, and 55.74 μg/mL, respectively. The low level of caffeine with a higher level of CGA correlates with their higher levels of NA inhibitory, as shown in the Garut samples. Therefore, the level of caffeine and CGA influenced the level of NA inhibitory activity. This is supported by the validation of CGA-NA binding interaction via molecular docking and pharmacophore modeling; hence, CGA could potentially serve as a bioactive compound for neuraminidase activity in GBAC.
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Alam S, Sarker MMR, Afrin S, Richi FT, Zhao C, Zhou JR, Mohamed IN. Traditional Herbal Medicines, Bioactive Metabolites, and Plant Products Against COVID-19: Update on Clinical Trials and Mechanism of Actions. Front Pharmacol 2021; 12:671498. [PMID: 34122096 PMCID: PMC8194295 DOI: 10.3389/fphar.2021.671498] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/06/2021] [Indexed: 12/11/2022] Open
Abstract
SARS-CoV-2 is the latest worldwide pandemic declared by the World Health Organization and there is no established anti-COVID-19 drug to combat this notorious situation except some recently approved vaccines. By affecting the global public health sector, this viral infection has created a disastrous situation associated with high morbidity and mortality rates along with remarkable cases of hospitalization because of its tendency to be high infective. These challenges forced researchers and leading pharmaceutical companies to find and develop cures for this novel strain of coronavirus. Besides, plants have a proven history of being notable wellsprings of potential drugs, including antiviral, antibacterial, and anticancer therapies. As a continuation of this approach, plant-based preparations and bioactive metabolites along with a notable number of traditional medicines, bioactive phytochemicals, traditional Chinese medicines, nutraceuticals, Ayurvedic preparations, and other plant-based products are being explored as possible therapeutics against COVID-19. Moreover, the unavailability of effective medicines against COVID-19 has driven researchers and members of the pharmaceutical, herbal, and related industries to conduct extensive investigations of plant-based products, especially those that have already shown antiviral properties. Even the recent invention of several vaccines has not eliminated doubts about safety and efficacy. As a consequence, many limited, unregulated clinical trials involving conventional mono- and poly-herbal therapies are being conducted in various areas of the world. Of the many clinical trials to establish such agents as credentialed sources of anti-COVID-19 medications, only a few have reached the landmark of completion. In this review, we have highlighted and focused on plant-based anti-COVID-19 clinical trials found in several scientific and authenticated databases. The aim is to allow researchers and innovators to identify promising and prospective anti-COVID-19 agents in clinical trials (either completed or recruiting) to establish them as novel therapies to address this unwanted pandemic.
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Affiliation(s)
- Safaet Alam
- Department of Pharmacy, State University of Bangladesh, Dhaka, Bangladesh
| | - Md. Moklesur Rahman Sarker
- Department of Pharmacy, State University of Bangladesh, Dhaka, Bangladesh
- Pharmacology and Toxicology Research Division, Health Med Science Research Limited, Dhaka, Bangladesh
| | - Sadia Afrin
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Fahmida Tasnim Richi
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Chao Zhao
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Jin-Rong Zhou
- Nutrition/Metabolism Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Isa Naina Mohamed
- Pharmacology Department, Medical Faculty, Universiti Kebangsaan Malaysia (The National University of Malaysia), Kuala Lumpur, Malaysia
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Das A, Pandita D, Jain GK, Agarwal P, Grewal AS, Khar RK, Lather V. Role of phytoconstituents in the management of COVID-19. Chem Biol Interact 2021; 341:109449. [PMID: 33798507 PMCID: PMC8008820 DOI: 10.1016/j.cbi.2021.109449] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 03/07/2021] [Accepted: 03/21/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND COVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas. SCOPE AND APPROACH This review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry through host cell receptors. The use of medicinal plants containing specific phytomoieties could be seen in providing a safer and long-term solution for the population with lesser side effects. Key Findings and Conclusions: Considering the high cost and time-consuming drug discovery process, therapeutic repositioning of existing drugs was explored as treatment option in COVID-19, however several molecules have been retracted as therapeutics either due to no positive outcomes or the severe side effects. These effects call for exploring the alternate treatment options which are therapeutically effective as well as safe. Keeping this in mind, phytopharmaceuticals derived from medicinal plants could be explored as important resources in the development of COVID-19 treatment, as their role in the past for treatment of viral diseases like HIV, MERS-CoV, and influenza has been well reported. Considering this fact, different phytoconstituents such as flavonoids, alkaloids, tannins and glycosides etc. Possessing antiviral properties against coronaviruses and possessing potential against SARS-CoV-2 have been reviewed in the present work.
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Affiliation(s)
- Amiya Das
- Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sector-125, Noida, 201313, India
| | - Deepti Pandita
- Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi, 110017, India.
| | - Gaurav Kumar Jain
- Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi, 110017, India
| | - Pallavi Agarwal
- Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sector-125, Noida, 201313, India
| | | | - Roop K Khar
- BS Anangpuria Institute of Pharmacy, Faridabad, Haryana, India
| | - Viney Lather
- Amity Institute of Pharmacy, Amity University Uttar Pradesh, Sector-125, Noida, 201313, India.
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Salgado-Albarrán M, Navarro-Delgado EI, Del Moral-Morales A, Alcaraz N, Baumbach J, González-Barrios R, Soto-Reyes E. Comparative transcriptome analysis reveals key epigenetic targets in SARS-CoV-2 infection. NPJ Syst Biol Appl 2021; 7:21. [PMID: 34031419 PMCID: PMC8144203 DOI: 10.1038/s41540-021-00181-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 03/08/2021] [Indexed: 02/04/2023] Open
Abstract
COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV, and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA, and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that has therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.
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Affiliation(s)
- Marisol Salgado-Albarrán
- grid.7220.70000 0001 2157 0393Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana-Cuajimalpa (UAM-C), Mexico City, Mexico ,grid.6936.a0000000123222966Chair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany
| | - Erick I. Navarro-Delgado
- grid.419167.c0000 0004 1777 1207Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Mexico City, Mexico
| | - Aylin Del Moral-Morales
- grid.7220.70000 0001 2157 0393Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana-Cuajimalpa (UAM-C), Mexico City, Mexico
| | - Nicolas Alcaraz
- grid.5254.60000 0001 0674 042XThe Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Jan Baumbach
- grid.9026.d0000 0001 2287 2617Chair of Computational Systems Biology, University of Hamburg, Hamburg, Germany ,grid.10825.3e0000 0001 0728 0170Computational BioMedicine Lab, Institute of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark
| | - Rodrigo González-Barrios
- grid.419167.c0000 0004 1777 1207Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Mexico City, Mexico
| | - Ernesto Soto-Reyes
- grid.7220.70000 0001 2157 0393Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana-Cuajimalpa (UAM-C), Mexico City, Mexico
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Keflie TS, Biesalski HK. Micronutrients and bioactive substances: Their potential roles in combating COVID-19. Nutrition 2021; 84:111103. [PMID: 33450678 PMCID: PMC7717879 DOI: 10.1016/j.nut.2020.111103] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 11/11/2020] [Accepted: 11/30/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVES The coronavirus disease 2019 (COVID-19) pandemic is seriously threatening public health and setting off huge economic crises across the world. In the absence of specific drugs for COVID-19, there is an urgent need to look for alternative approaches. Therefore, the aim of this paper was to review the roles of micronutrients and bioactive substances as potential alternative approaches in combating COVID-19. METHODS This review was based on the literature identified using electronic searches in different databases. RESULTS Vitamins (A, B, C, D, and E), minerals (selenium and zinc), and bioactive substances from curcumin, echinacea, propolis, garlic, soybean, green tea, and other polyphenols were identified as having potential roles in interfering with spike glycoproteins, angiotensin converting enzyme 2, and transmembrane protease serine 2 at the entry site, and inhibiting activities of papain-like protease, 3 chymotrypsin-like protease, and RNA-dependent RNA polymerase in the replication cycle of severe acute respiratory syndrome coronavirus 2. Having immunomodulating, antiinflammatory, antioxidant, and antiviral properties, such micronutrients and bioactive substances are consequently promising alterative nutritional approaches to combat COVID-19. CONCLUSIONS The roles of micronutrients and bioactive substances in the fight against COVID-19 are exciting areas of research. This review may suggest directions for further study.
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Yang HC, Ma TH, Tjong WY, Stern A, Chiu DTY. G6PD deficiency, redox homeostasis, and viral infections: implications for SARS-CoV-2 (COVID-19). Free Radic Res 2021; 55:364-374. [PMID: 33401987 PMCID: PMC7799378 DOI: 10.1080/10715762.2020.1866757] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/08/2020] [Accepted: 12/10/2020] [Indexed: 02/08/2023]
Abstract
The COVID-19 pandemic has so far affected more than 45 million people and has caused over 1 million deaths worldwide. Infection with SARS-CoV-2, the pathogenic agent, which is associated with an imbalanced redox status, causes hyperinflammation and a cytokine storm, leading to cell death. Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals may experience a hemolytic crisis after being exposed to oxidants or infection. Individuals with G6PD deficiency are more susceptible to coronavirus infection than individuals with normally functioning G6PD. An altered immune response to viral infections is found in individuals with G6PD deficiency. Evidence indicates that G6PD deficiency is a predisposing factor of COVID-19.
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Affiliation(s)
- Hung-Chi Yang
- Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsinchu, Taiwan
| | - Tian-Hsiang Ma
- Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Wen-Ye Tjong
- Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Arnold Stern
- Grossman School of Medicine, New York University, New York, NY, USA
| | - Daniel Tsun-Yee Chiu
- Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
- Department of Pediatric Hematology/Oncology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
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Abstract
Influenza A virus (IAV) causes seasonal epidemics annually and pandemics every few decades. Most antiviral treatments used for IAV are only effective if administered during the first 48 h of infection and antiviral resistance is possible. Therapies that can be initiated later during IAV infection and that are less likely to elicit resistance will significantly improve treatment options. Pyruvate, a key metabolite, and an end product of glycolysis, has been studied for many uses, including its anti-inflammatory capabilities. Sodium pyruvate was recently shown by us to decrease inflammasome activation during IAV infection. Here, we investigated sodium pyruvate’s effects on IAV in vivo. We found that nebulizing mice with sodium pyruvate decreased morbidity and weight loss during infection. Additionally, treated mice consumed more chow during infection, indicating improved symptoms. There were notable improvements in pro-inflammatory cytokine production (IL-1β) and lower virus titers on day 7 post-infection in mice treated with sodium pyruvate compared to control animals. As pyruvate acts on the host immune response and metabolic pathways and not directly on the virus, our data demonstrate that sodium pyruvate is a promising treatment option that is safe, effective, and unlikely to elicit antiviral resistance.
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Wu YH, Yeh IJ, Phan NN, Yen MC, Hung JH, Chiao CC, Chen CF, Sun Z, Hsu HP, Wang CY, Lai MD. Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2021; 54:845-857. [PMID: 34176764 PMCID: PMC7997684 DOI: 10.1016/j.jmii.2021.03.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 12/03/2020] [Accepted: 03/07/2021] [Indexed: 12/23/2022]
Abstract
Background Pathogenic coronaviruses include Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2. These viruses have induced outbreaks worldwide, and there are currently no effective medications against them. Therefore, there is an urgent need to develop potential drugs against coronaviruses. Methods High-throughput technology is widely used to explore differences in messenger (m)RNA and micro (mi)RNA expression profiles, especially to investigate protein–protein interactions and search for new therapeutic compounds. We integrated miRNA and mRNA expression profiles in MERS-CoV-infected cells and compared them to mock-infected controls from public databases. Results Through the bioinformatics analysis, there were 251 upregulated genes and eight highly differentiated miRNAs that overlapped in the two datasets. External validation verified that these genes had high expression in MERS-CoV-infected cells, including RC3H1, NF-κB, CD69, TNFAIP3, LEAP-2, DUSP10, CREB5, CXCL2, etc. We revealed that immune, olfactory or sensory system-related, and signal-transduction networks were discovered from upregulated mRNAs in MERS-CoV-infected cells. In total, 115 genes were predicted to be related to miRNAs, with the intersection of upregulated mRNAs and miRNA-targeting prediction genes such as TCF4, NR3C1, and POU2F2. Through the Connectivity Map (CMap) platform, we suggested potential compounds to use against MERS-CoV infection, including diethylcarbamazine, harpagoside, bumetanide, enalapril, and valproic acid. Conclusions The present study illustrates the crucial roles of miRNA-mRNA interacting networks in MERS-CoV-infected cells. The genes we identified are potential targets for treating MERS-CoV infection; however, these could possibly be extended to other coronavirus infections.
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Affiliation(s)
- Yen-Hung Wu
- Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - I-Jeng Yeh
- Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Nam Nhut Phan
- NTT Institute of Hi-Technology, Nguyen Tat Thanh University, Ho Chi Minh City, Viet Nam
| | - Meng-Chi Yen
- Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Jui-Hsiang Hung
- Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan
| | - Chung-Chieh Chiao
- School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan
| | - Chien-Fu Chen
- School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan
| | - Zhengda Sun
- Kaiser Permanente, Northern California Regional Laboratories, The Permanente Medical Group, 1725 Eastshore Hwy, Berkeley, CA 94710, USA
| | - Hui-Ping Hsu
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN37232, USA.
| | - Chih-Yang Wang
- Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
| | - Ming-Derg Lai
- Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan 70101, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
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Teodoro JS, Machado IF, Castela AC, Rolo AP, Palmeira CM. Mitochondria as a target for safety and toxicity evaluation of nutraceuticals. NUTRACEUTICALS 2021:463-483. [DOI: 10.1016/b978-0-12-821038-3.00030-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Olaleye O, Titilope O, Moses O. Possible health benefits of polyphenols in neurological disorders associated with COVID-19. ACTA FACULTATIS MEDICAE NAISSENSIS 2021. [DOI: 10.5937/afmnai38-30190] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Novel Coronavirus disease 2019 (COVID-19) represents an emergent global health burden that has challenged the health systems worldwide. Since its sudden upsurge in 2019, many COVID-19 patients have exhibited neurological symptoms and complications. Till now, there is no known effective established drug against the highly contagious COVID-19 infection despite the frightening associated mortality rate. This article aims to present the mechanism of action of coronavirus-2 (SARS-CoV-2), the clinical neurological manifestations displayed by COVID-19 patients, and present polyphenols with neuroprotective ability that can offer beneficial effects against COVID-19-mediated neuropathology. Reports from COVID-19 clinical studies, case reports, and other related literature were evaluated for this review. Neurological complications of COVID-19 include anosmia, acute cerebrovascular disease, acute disseminated post-infectious encephalomyelitis, encephalitis, etc. Also, SARS-CoV-2 sould be a neurotropic vіruѕ due to its iѕolatіon from serebroѕrіnal fluіd. Multіrle neurologіsal damages displayed by COVID-19 patients might be due to hyperinflammation associated with SARS-CoV-2 infections. Resveratrol, kolaviron, quercetin and apigenin are polyphenols with proven anti-inflammatory and therapeutic properties that can extenuate the adverse effects of COVID-19. These polyphenols have been documented to suppress c-Jun N-terminal kinase (JNK), phosphoinositide-3-kinase (PI3-K), extrasellularѕіgnal-regulated kinase (ERK), nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB) and mіtogen-astіvated protein kіnaѕe (MAPK) pathways which are essential in the pathogenesis of COVID-19. They also showed significant inhibitory activities against SARS-CoV-2 proteins. Taken together, these polyphenols may offer neuroprotective benefits against COVID-19 mediated neuropathology via modulation of the pathogenic pathways.
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Evidence of TCM Theory in Treating the Same Disease with Different Methods: Treatment of Pneumonia with Ephedra sinica and Scutellariae Radix as an Example. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:8873371. [PMID: 33354223 PMCID: PMC7737398 DOI: 10.1155/2020/8873371] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/20/2020] [Accepted: 10/20/2020] [Indexed: 12/22/2022]
Abstract
Pneumonia is a serious global health problem and the leading cause of mortality in children. Antibiotics are the main treatment for bacterial pneumonia, but there are serious drug resistance problems. Traditional Chinese medicine (TCM) has been used to treat diseases for thousands of years and has a unique theory. This article takes the treatment of pneumonia with Ephedra sinica as a representative hot medicine and Scutellariae Radix as a representative cold medicine as an example. We explore and explain the theory of treating the same disease with different TCM treatments. Using transcriptomics and network pharmacology methods, GO, KEGG enrichment, and PPI network construction were carried out, demonstrating that Ephedra sinica plays a therapeutic role through the NF-κB and apoptosis signaling pathways targeting PLAU, CD40LG, BLC2L1, CASP7, and CXCL8. The targets of Scutellariae Radix through the IL-17 signaling pathway are MMP9, CXCL8, and MAPK14. Molecular docking technology was also used to verify the results. In short, our results provide evidence for the theory of treating the same disease with different treatments, and we also discuss future directions for traditional Chinese medicine.
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Preventive Effect of a Polyphenol-Rich Extract from Geranium sanguineum L. on Hepatic Drug Metabolism in Influenza Infected Mice. Sci Pharm 2020. [DOI: 10.3390/scipharm88040045] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The decreased hepatic drug metabolism (predominately first phase) is one of the essential reasons for numerous side effects and for increased drug toxicity during influenza virus infection (IVI). The present study aims to investigate some mechanisms of the preventive effect of a standardized polyphenol complex from the medicinal plant Geranium sanguineum L. (PPhC) (10 mg/kg nasally). A verified experimental model of IVI A/Aichi/2/68 (H3N2) (4.5 lg LD50) in male ICR (Institute of Cancer Research, USA) mice was used. Changes in hepatic monooxygenase activities as well as nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome C reductase activity and cytochtome P450 content were studied on days 2, 6, 9, 21 of the infection together with thiobarbituric acid reactive substances in the liver supernatant. Our data clearly demonstrates that IVI affects all components of the electronic chain of cytochrome P-450. N-demethylases and hydroxylases as well as the activity of cytochrome C reductase and cytochtome P-450 content were decreased in the course of the virus infection. This implies that free radicals play an important role not only in the pathogenesis of IVI, but also in the modulation of the hepatic monooxygenase activity. This is also consistent with the established polyphenol complex PPhC from the medicinal plant Geranium sanguineum L. preventive effect against increased thiobarbituric acid reactive substances (TBARS)-levels. PPhC restored most of the monooxygenase activities that were inhibited in IVI animals, even over the control levels, probably via multiple mechanisms that may entail antioxidant activity and selective antiviral and protein-binding effects. In contrast to infected animals, in healthy mice, PPhC showed moderate reversible inhibitory effect on hepatic monooxygenase activities.
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Hecel A, Ostrowska M, Stokowa-Sołtys K, Wątły J, Dudek D, Miller A, Potocki S, Matera-Witkiewicz A, Dominguez-Martin A, Kozłowski H, Rowińska-Żyrek M. Zinc(II)-The Overlooked Éminence Grise of Chloroquine's Fight against COVID-19? Pharmaceuticals (Basel) 2020; 13:E228. [PMID: 32882888 PMCID: PMC7558363 DOI: 10.3390/ph13090228] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 08/28/2020] [Accepted: 08/29/2020] [Indexed: 12/24/2022] Open
Abstract
Zn(II) is an inhibitor of SARS-CoV-2's RNA-dependent RNA polymerase, and chloroquine and hydroxychloroquine are Zn(II) ionophores-this statement gives a curious mind a lot to think about. We show results of the first clinical trials on chloroquine (CQ) and hydroxychloroquine (HCQ) in the treatment of COVID-19, as well as earlier reports on the anticoronaviral properties of these two compounds and of Zn(II) itself. Other FDA-approved Zn(II) ionophores are given a decent amount of attention and are thought of as possible COVID-19 therapeutics.
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Affiliation(s)
- Aleksandra Hecel
- Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland; (A.H.); (M.O.); (K.S.-S.); (J.W.); (D.D.); (A.M.); (S.P.); (H.K.)
| | - Małgorzata Ostrowska
- Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland; (A.H.); (M.O.); (K.S.-S.); (J.W.); (D.D.); (A.M.); (S.P.); (H.K.)
| | - Kamila Stokowa-Sołtys
- Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland; (A.H.); (M.O.); (K.S.-S.); (J.W.); (D.D.); (A.M.); (S.P.); (H.K.)
| | - Joanna Wątły
- Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland; (A.H.); (M.O.); (K.S.-S.); (J.W.); (D.D.); (A.M.); (S.P.); (H.K.)
| | - Dorota Dudek
- Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland; (A.H.); (M.O.); (K.S.-S.); (J.W.); (D.D.); (A.M.); (S.P.); (H.K.)
| | - Adriana Miller
- Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland; (A.H.); (M.O.); (K.S.-S.); (J.W.); (D.D.); (A.M.); (S.P.); (H.K.)
| | - Sławomir Potocki
- Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland; (A.H.); (M.O.); (K.S.-S.); (J.W.); (D.D.); (A.M.); (S.P.); (H.K.)
| | - Agnieszka Matera-Witkiewicz
- Screening Laboratory of Biological Activity Tests and Collection of Biological Material, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland;
| | - Alicia Dominguez-Martin
- Department of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, E-18071 Granada, Spain;
| | - Henryk Kozłowski
- Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland; (A.H.); (M.O.); (K.S.-S.); (J.W.); (D.D.); (A.M.); (S.P.); (H.K.)
- Department of Physiotherapy, Opole Medical School, Katowicka 68, 40-060 Opole, Poland
| | - Magdalena Rowińska-Żyrek
- Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland; (A.H.); (M.O.); (K.S.-S.); (J.W.); (D.D.); (A.M.); (S.P.); (H.K.)
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Zima V, Radilová K, Kožíšek M, Albiñana CB, Karlukova E, Brynda J, Fanfrlík J, Flieger M, Hodek J, Weber J, Majer P, Konvalinka J, Machara A. Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors. Eur J Med Chem 2020; 208:112754. [PMID: 32883638 DOI: 10.1016/j.ejmech.2020.112754] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 07/20/2020] [Accepted: 08/09/2020] [Indexed: 01/27/2023]
Abstract
The biological effects of flavonoids on mammal cells are diverse, ranging from scavenging free radicals and anti-cancer activity to anti-influenza activity. Despite appreciable effort to understand the anti-influenza activity of flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. Here, we report the development and validation of a screening assay based on AlphaScreen technology and illustrate its application for determination of the inhibitory potency of a large set of polyols against PA N-terminal domain (PA-Nter) of influenza RNA-dependent RNA polymerase featuring endonuclease activity. The most potent inhibitors we identified were luteolin with an IC50 of 72 ± 2 nM and its 8-C-glucoside orientin with an IC50 of 43 ± 2 nM. Submicromolar inhibitors were also evaluated by an in vitro endonuclease activity assay using single-stranded DNA, and the results were in full agreement with data from the competitive AlphaScreen assay. Using X-ray crystallography, we analyzed structures of the PA-Nter in complex with luteolin at 2.0 Å resolution and quambalarine B at 2.5 Å resolution, which clearly revealed the binding pose of these polyols coordinated to two manganese ions in the endonuclease active site. Using two distinct assays along with the structural work, we have presumably identified and characterized the molecular mode-of-action of flavonoids in influenza-infected cells.
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Affiliation(s)
- Václav Zima
- Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 00, Prague 2, Czech Republic; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic
| | - Kateřina Radilová
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic; First Faculty of Medicine, Charles University, Kateřinská 1660, 121 08, Prague 2, Czech Republic
| | - Milan Kožíšek
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic.
| | - Carlos Berenguer Albiñana
- Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 00, Prague 2, Czech Republic; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic
| | - Elena Karlukova
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic
| | - Jiří Brynda
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic; Institute of Molecular Genetics of the Czech Academy of Sciences, Vídeňská 1083, 140 00, Prague 4, Czech Republic
| | - Jindřich Fanfrlík
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic
| | - Miroslav Flieger
- Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 140 00, Prague 4, Czech Republic
| | - Jan Hodek
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic
| | - Jan Weber
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic
| | - Pavel Majer
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic
| | - Jan Konvalinka
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic; Department of Biochemistry, Faculty of Science, Charles University, Hlavova 8, 128 00, Prague 2, Czech Republic
| | - Aleš Machara
- Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 00, Prague 2, Czech Republic; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10, Prague 6, Czech Republic.
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45
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Siqueira IR, Simões CMO, Bassani VL. Achyrocline satureioides (Lam.) D.C. as a potential approach for management of viral respiratory infections. Phytother Res 2020; 35:3-5. [PMID: 32757241 PMCID: PMC7436611 DOI: 10.1002/ptr.6807] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 06/22/2020] [Accepted: 06/24/2020] [Indexed: 11/12/2022]
Affiliation(s)
- Ionara Rodrigues Siqueira
- Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Cláudia Maria Oliveira Simões
- Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - Valquiria Linck Bassani
- Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Santa Catarina, Brazil
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Chen KK, Minakuchi M, Wuputra K, Ku CC, Pan JB, Kuo KK, Lin YC, Saito S, Lin CS, Yokoyama KK. Redox control in the pathophysiology of influenza virus infection. BMC Microbiol 2020; 20:214. [PMID: 32689931 PMCID: PMC7370268 DOI: 10.1186/s12866-020-01890-9] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 07/01/2020] [Indexed: 01/07/2023] Open
Abstract
Triggered in response to external and internal ligands in cells and animals, redox homeostasis is transmitted via signal molecules involved in defense redox mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Cellular oxidation is not necessarily harmful per se, but its effects depend on the balance between the peroxidation and antioxidation cascades, which can vary according to the stimulus and serve to maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and redox control using IV infection as an example. We discuss the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS accumulation and the diversity of IV infection. We also summarize the potential anti-IV agents available currently that act by targeting redox biology/pathophysiology.
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Affiliation(s)
- Ker-Kong Chen
- School of Dentistry, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
- Department of Densitory, Kaohisung University Hospital, Kaohisung, 807, Taiwan
| | - Moeko Minakuchi
- Waseda Research Institute for Science and Engineering, Waseca University, Shinjuku, Tokyo, 162-8480, Japan
| | - Kenly Wuputra
- Graduate Institute of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Rd., San-Ming District, Kaohsiung, 80807, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
| | - Chia-Chen Ku
- Graduate Institute of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Rd., San-Ming District, Kaohsiung, 80807, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
| | - Jia-Bin Pan
- Graduate Institute of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Rd., San-Ming District, Kaohsiung, 80807, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
| | - Kung-Kai Kuo
- Department Surgery, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan
| | - Ying-Chu Lin
- School of Dentistry, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
| | - Shigeo Saito
- Waseda Research Institute for Science and Engineering, Waseca University, Shinjuku, Tokyo, 162-8480, Japan
- Saito Laboratory of Cell Technology Institute, Yalta, Tochigi, 329-1471, Japan
| | - Chang-Shen Lin
- Graduate Institute of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Rd., San-Ming District, Kaohsiung, 80807, Taiwan.
- Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan.
| | - Kazunari K Yokoyama
- Waseda Research Institute for Science and Engineering, Waseca University, Shinjuku, Tokyo, 162-8480, Japan.
- Graduate Institute of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Rd., San-Ming District, Kaohsiung, 80807, Taiwan.
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan.
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Abuo-Rahma GEDA, Mohamed MFA, Ibrahim TS, Shoman ME, Samir E, Abd El-Baky RM. Potential repurposed SARS-CoV-2 (COVID-19) infection drugs. RSC Adv 2020; 10:26895-26916. [PMID: 35515773 PMCID: PMC9055522 DOI: 10.1039/d0ra05821a] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 07/08/2020] [Indexed: 01/09/2023] Open
Abstract
The global outbreak of COVID-19 viral infection is associated with the absence of specific drug(s) for fighting this viral infection. About 10 million people are already infected, about 500 000 deaths all over the world to date. Great efforts have been made to find solutions for this viral infection, either vaccines, monoclonal antibodies, or small molecule drugs; this can stop the spread of infection to avoid the expected human, economic and social catastrophe associated with this infection. In the literature and during clinical trials in hospitals, several FDA approved drugs for different diseases have the potential to treat or reduce the severity of COVID-19. Repurposing of these drugs as potential agents to treat COVID-19 reduces the time and cost to find effective COVID-19 agents. This review article summarizes the present situation of transmission, pathogenesis and statistics of COVID-19 in the world. Moreover, it includes chemistry, mechanism of action at the molecular level of the possible drug molecules which are liable for redirection as potential COVID-19 therapeutic agents. This includes polymerase inhibitors, protease inhibitors, malaria drugs, lipid lowering statins, rheumatoid arthritis drugs and some miscellaneous agents. We offer research data and knowledge about the chemistry and biology of potential COVID-19 drugs for the research community in this field.
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Affiliation(s)
- Gamal El-Din A Abuo-Rahma
- Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University 61519 Minia Egypt +20 1003069431
| | - Mamdouh F A Mohamed
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University 82524 Sohag Egypt
| | - Tarek S Ibrahim
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University Jeddah 21589 Saudi Arabia
- Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University Zagazig 44519 Egypt
| | - Mai E Shoman
- Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University 61519 Minia Egypt +20 1003069431
| | - Ebtihal Samir
- Physical Chemistry, Department of Analytical Chemistry, Faculty of Pharmacy, Deraya University Minia 11566 Egypt
| | - Rehab M Abd El-Baky
- Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University 61519 Minia Egypt
- Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University Minia 11566 Egypt
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Colunga Biancatelli RML, Berrill M, Catravas JD, Marik PE. Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19). Front Immunol 2020; 11:1451. [PMID: 32636851 PMCID: PMC7318306 DOI: 10.3389/fimmu.2020.01451] [Citation(s) in RCA: 295] [Impact Index Per Article: 59.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 06/04/2020] [Indexed: 12/25/2022] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose antiviral properties have been investigated in numerous studies. There is evidence that vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties and the capacity of ascorbate to recycle quercetin, increasing its efficacy. Safe, cheap interventions which have a sound biological rationale should be prioritized for experimental use in the current context of a global health pandemic. We present the current evidence for the use of vitamin C and quercetin both for prophylaxis in high-risk populations and for the treatment of COVID-19 patients as an adjunct to promising pharmacological agents such as Remdesivir or convalescent plasma.
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Affiliation(s)
- Ruben Manuel Luciano Colunga Biancatelli
- Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA, United States
- Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, United States
- Policlinico Umberto I, La Sapienza University of Rome, Rome, Italy
| | - Max Berrill
- Department of Respiratory Medicine, St. Peter's Hospital, Surrey, United Kingdom
| | - John D. Catravas
- Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA, United States
- Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, United States
- School of Medical Diagnostic & Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, VA, United States
| | - Paul E. Marik
- Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA, United States
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Checconi P, De Angelis M, Marcocci ME, Fraternale A, Magnani M, Palamara AT, Nencioni L. Redox-Modulating Agents in the Treatment of Viral Infections. Int J Mol Sci 2020; 21:E4084. [PMID: 32521619 PMCID: PMC7312898 DOI: 10.3390/ijms21114084] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 06/01/2020] [Accepted: 06/05/2020] [Indexed: 12/27/2022] Open
Abstract
Viruses use cell machinery to replicate their genome and produce viral proteins. For this reason, several intracellular factors, including the redox state, might directly or indirectly affect the progression and outcome of viral infection. In physiological conditions, the redox balance between oxidant and antioxidant species is maintained by enzymatic and non-enzymatic systems, and it finely regulates several cell functions. Different viruses break this equilibrium and induce an oxidative stress that in turn facilitates specific steps of the virus lifecycle and activates an inflammatory response. In this context, many studies highlighted the importance of redox-sensitive pathways as novel cell-based targets for therapies aimed at blocking both viral replication and virus-induced inflammation. In the review, we discuss the most recent findings in this field. In particular, we describe the effects of natural or synthetic redox-modulating molecules in inhibiting DNA or RNA virus replication as well as inflammatory pathways. The importance of the antioxidant transcription factor Nrf2 is also discussed. Most of the data reported here are on influenza virus infection. We believe that this approach could be usefully applied to fight other acute respiratory viral infections characterized by a strong inflammatory response, like COVID-19.
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Affiliation(s)
- Paola Checconi
- IRCCS San Raffaele Pisana, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy; (P.C.); (A.T.P.)
| | - Marta De Angelis
- Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy; (M.D.A.); (M.E.M.)
| | - Maria Elena Marcocci
- Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy; (M.D.A.); (M.E.M.)
| | - Alessandra Fraternale
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino (PU), Italy; (A.F.); (M.M.)
| | - Mauro Magnani
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino (PU), Italy; (A.F.); (M.M.)
| | - Anna Teresa Palamara
- IRCCS San Raffaele Pisana, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy; (P.C.); (A.T.P.)
- Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy; (M.D.A.); (M.E.M.)
| | - Lucia Nencioni
- Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy; (M.D.A.); (M.E.M.)
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50
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Ulomskiy EN, Ivanova AV, Gorbunov EB, Esaulkova IL, Slita AV, Sinegubova EO, Voinkov EK, Drokin RA, Butorin II, Gazizullina ER, Gerasimova EL, Zarubaev VV, Rusinov VL. Synthesis and biological evaluation of 6-nitro-1,2,4-triazoloazines containing polyphenol fragments possessing antioxidant and antiviral activity. Bioorg Med Chem Lett 2020; 30:127216. [PMID: 32360104 DOI: 10.1016/j.bmcl.2020.127216] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 04/23/2020] [Accepted: 04/24/2020] [Indexed: 01/07/2023]
Abstract
Stable σ-adducts of azolo[5,1-c]triazines and azolo[1,5-a]pyrimidines with different polyphenols were synthesized and their antioxidant and antiviral activity were investigated. Their affinity to viral hemagglutinin was assessed using molecular modelling. The phloroglucinol-modified azolo-azines possessed the highest virus-inhibiting activity. According to the results of the study of antioxidant properties of compounds, the most promising ones exhibiting highest antioxidant capacity were adducts containing in their structure pyrogallol and catechol residues and 6-nitro-triazolotriazin-7-ol scaffold. No correlation between antioxidant and virus-inhibiting activity of compounds studied was detected. The most active compounds demonstrated the ability to prevent binding of viral hemagglutinin with cellular receptor as shown in hemagglutination inhibition assay. Our results demonstrate that polyphenol-modified azolo-azines are prospective for further optimization as potential antivirals and that their action is directed against viral hemagglutinin.
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Affiliation(s)
- E N Ulomskiy
- Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Organic and Biomolecular Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation; Institute of Organic Synthesis, Ural Division of RAS, 620990, 22/20 S. Kovalevskoy st./Akademicheskaya st., Yekaterinburg, Russian Federation
| | - A V Ivanova
- Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Analytical Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation
| | - E B Gorbunov
- Institute of Organic Synthesis, Ural Division of RAS, 620990, 22/20 S. Kovalevskoy st./Akademicheskaya st., Yekaterinburg, Russian Federation
| | - I L Esaulkova
- Pasteur Institute for Epidemiology and Microbiology, 197101, 14 Mira st., Saint Petersburg, Russian Federation
| | - A V Slita
- Pasteur Institute for Epidemiology and Microbiology, 197101, 14 Mira st., Saint Petersburg, Russian Federation
| | - E O Sinegubova
- Pasteur Institute for Epidemiology and Microbiology, 197101, 14 Mira st., Saint Petersburg, Russian Federation
| | - E K Voinkov
- Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Organic and Biomolecular Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation
| | - R A Drokin
- Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Organic and Biomolecular Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation
| | - I I Butorin
- Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Organic and Biomolecular Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation
| | - E R Gazizullina
- Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Analytical Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation
| | - E L Gerasimova
- Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Analytical Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation
| | - V V Zarubaev
- Pasteur Institute for Epidemiology and Microbiology, 197101, 14 Mira st., Saint Petersburg, Russian Federation.
| | - V L Rusinov
- Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Organic and Biomolecular Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation; Institute of Organic Synthesis, Ural Division of RAS, 620990, 22/20 S. Kovalevskoy st./Akademicheskaya st., Yekaterinburg, Russian Federation
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