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Sotoudeheian M, Mirahmadi SMS, Pirhayati M, Farahmandian N, Azarbad R, Toroudi HP. Targeting SIRT1 by Scopoletin to Inhibit XBB.1.5 COVID-19 Life Cycle. Curr Rev Clin Exp Pharmacol 2025; 20:4-13. [PMID: 38441021 DOI: 10.2174/0127724328281178240225082456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 12/21/2023] [Accepted: 01/05/2024] [Indexed: 03/06/2024]
Abstract
Natural products have historically driven pharmaceutical discovery, but their reliance has diminished with synthetic drugs. Approximately 35% of medicines originate from natural products. Scopoletin, a natural coumarin compound found in herbs, exhibits antioxidant, hepatoprotective, antiviral, and antimicrobial properties through diverse intracellular signaling mechanisms. Furthermore, it also enhances the activity of antioxidants. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes viral pneumonia through cytokine storms and systemic inflammation. Cellular autophagy pathways play a role in coronavirus replication and inflammation. The Silent Information Regulator 1 (SIRT1) pathway, linked to autophagy, protects cells via FOXO3, inhibits apoptosis, and modulates SIRT1 in type-II epithelial cells. SIRT1 activation by adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) enhances the autophagy cascade. This pathway holds therapeutic potential for alveolar and pulmonary diseases and is crucial in lung inflammation. Angiotensin-converting enzyme 2 (ACE-2) activation, inhibited by reduced expression, prevents COVID-19 virus entry into type-II epithelial cells. The coronavirus disease 2019 (COVID-19) virus binds ACE-2 to enter into the host cells, and XBB.1.5 COVID-19 displays high ACE-2-binding affinity. ACE-2 expression in pneumocytes is regulated by signal transducers and activators of transcription-3 (STAT3), which can increase COVID-19 virus replication. SIRT1 regulates STAT3, and the SIRT1/STAT3 pathway is involved in lung diseases. Therapeutic regulation of SIRT1 protects the lungs from inflammation caused by viral-mediated oxidative stress. Scopoletin, as a modulator of the SIRT1 cascade, can regulate autophagy and inhibit the entry and life cycle of XBB.1.5 COVID-19 in host cells.
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Affiliation(s)
| | | | | | - Navid Farahmandian
- Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Azarbad
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Hamidreza Pazoki Toroudi
- Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Chen P, Wu M, He Y, Jiang B, He ML. Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection. Signal Transduct Target Ther 2023; 8:237. [PMID: 37286535 DOI: 10.1038/s41392-023-01510-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 04/18/2023] [Accepted: 05/19/2023] [Indexed: 06/09/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2 infection has become a global pandemic due to the high viral transmissibility and pathogenesis, bringing enormous burden to our society. Most patients infected by SARS-CoV-2 are asymptomatic or have mild symptoms. Although only a small proportion of patients progressed to severe COVID-19 with symptoms including acute respiratory distress syndrome (ARDS), disseminated coagulopathy, and cardiovascular disorders, severe COVID-19 is accompanied by high mortality rates with near 7 million deaths. Nowadays, effective therapeutic patterns for severe COVID-19 are still lacking. It has been extensively reported that host metabolism plays essential roles in various physiological processes during virus infection. Many viruses manipulate host metabolism to avoid immunity, facilitate their own replication, or to initiate pathological response. Targeting the interaction between SARS-CoV-2 and host metabolism holds promise for developing therapeutic strategies. In this review, we summarize and discuss recent studies dedicated to uncovering the role of host metabolism during the life cycle of SARS-CoV-2 in aspects of entry, replication, assembly, and pathogenesis with an emphasis on glucose metabolism and lipid metabolism. Microbiota and long COVID-19 are also discussed. Ultimately, we recapitulate metabolism-modulating drugs repurposed for COVID-19 including statins, ASM inhibitors, NSAIDs, Montelukast, omega-3 fatty acids, 2-DG, and metformin.
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Affiliation(s)
- Peiran Chen
- Department of Biomedical Sciences, City University of Hong Kong, HKSAR, Hong Kong, China
| | - Mandi Wu
- Department of Biomedical Sciences, City University of Hong Kong, HKSAR, Hong Kong, China
| | - Yaqing He
- Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, Guangdong, China
| | - Binghua Jiang
- Cell Signaling and Proteomic Center, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Ming-Liang He
- Department of Biomedical Sciences, City University of Hong Kong, HKSAR, Hong Kong, China.
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A Systematic Review on the Safety and Efficacy of COVID-19 Vaccines Approved in Saudi Arabia. Vaccines (Basel) 2023; 11:vaccines11020281. [PMID: 36851158 PMCID: PMC9962734 DOI: 10.3390/vaccines11020281] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/18/2023] [Accepted: 01/26/2023] [Indexed: 01/31/2023] Open
Abstract
Comprehensive safety and efficacy studies of COVID-19 vaccines might reduce the apprehension of the general population about the adverse reactions and duration of protection offered by them. The study aimed to conduct a systemic review on the four COVID-19 vaccines (AstraZeneca, Pfizer, Moderna, and Janssen) approved in Saudi Arabia. The study was conducted by reviewing the published articles from electronic databases such as PubMed, Embase, Cochrane Library and Web of Science using the search terms "COVID-19", "Vaccine", "Safety", "Efficacy" and "Human trials" and as per the standard guidelines for systemic review. The review analyzed eighteen articles and the data from them were evaluated to analyze the safety and efficacy of the vaccines in different groups of population such as males, females, those above 18 years and people with co-morbidities. The common local reactions observed after vaccination were pain at the site of injection (40-70%), redness (16-30%), swelling (18-39%) and tenderness (20-40%). The systemic reactions reported were fever (40-60%), chills (12-23%), fatigue (44-65%), headache (30-42%) and muscle pain (15-40%). The efficacy was observed to be above the threshold value (60%) stipulated by the WHO. However, precautions need to be followed while vaccinating special groups of population such as those that are pregnant, lactating or experiencing severe illness. Additionally, the rare and serious adverse events reported remotely after vaccination need more studies.
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Li H, Li X, Wu Q, Wang X, Qin Z, Wang Y, He Y, Wu Q, Li L, Chen H. Plasma proteomic and metabolomic characterization of COVID-19 survivors 6 months after discharge. Cell Death Dis 2022; 13:235. [PMID: 35288537 PMCID: PMC8919172 DOI: 10.1038/s41419-022-04674-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 02/11/2022] [Accepted: 02/18/2022] [Indexed: 02/08/2023]
Abstract
Coronavirus disease 2019 (COVID-19) has gained prominence as a global pandemic. Studies have suggested that systemic alterations persist in a considerable proportion of COVID-19 patients after hospital discharge. We used proteomic and metabolomic approaches to analyze plasma samples obtained from 30 healthy subjects and 54 COVID-19 survivors 6 months after discharge from the hospital, including 30 non-severe and 24 severe patients. Through this analysis, we identified 1019 proteins and 1091 metabolites. The differentially expressed proteins and metabolites were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Among the patients evaluated, 41% of COVID-19 survivors reported at least one clinical symptom and 26.5% showed lung imaging abnormalities at 6 months after discharge. Plasma proteomics and metabolomics analysis showed that COVID-19 survivors differed from healthy control subjects in terms of the extracellular matrix, immune response, and hemostasis pathways. COVID-19 survivors also exhibited abnormal lipid metabolism, disordered immune response, and changes in pulmonary fibrosis-related proteins. COVID-19 survivors show persistent proteomic and metabolomic abnormalities 6 months after discharge from the hospital. Hence, the recovery period for COVID-19 survivors may be longer.
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Affiliation(s)
- Hongwei Li
- Department of Respiratory Medicine, Haihe Hospital, Tianjin University, Tianjin, China
| | - Xue Li
- Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin, China
- Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin, China
| | - Qian Wu
- Department of Respiratory Medicine, Haihe Hospital, Tianjin University, Tianjin, China
| | - Xing Wang
- Department of Respiratory Medicine, Haihe Hospital, Tianjin University, Tianjin, China
| | - Zhonghua Qin
- Department of Laboratory Medicine, Haihe Hospital, Tianjin University, Tianjin, China
| | - Yaguo Wang
- Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Yanbin He
- Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Qi Wu
- Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin, China.
| | - Li Li
- Department of Respiratory Medicine, Haihe Hospital, Tianjin University, Tianjin, China.
- Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin, China.
| | - Huaiyong Chen
- Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin, China.
- Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin, China.
- Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin, China.
- Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin, China.
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Lu ZH, Yu WL, Sun Y. Multiple immune function impairments in diabetic patients and their effects on COVID-19. World J Clin Cases 2021; 9:6969-6978. [PMID: 34540952 PMCID: PMC8409204 DOI: 10.12998/wjcc.v9.i24.6969] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/18/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, poses a significant threat to public health worldwide, and diabetes is considered a risk factor for the rapid progression and poor prognosis of COVID-19. Limited immune function is a clinical feature of COVID-19 patients, and diabetes patients have defects in innate and adaptive immune functions, which may be an important reason for the rapid progression and poor prognosis of COVID-19 in patients with diabetes. We review the possible multiple effects of immune impairment in diabetic patients on the immune responses to COVID-19 to provide guidance for the diagnosis and treatment of diabetic patients with COVID-19.
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Affiliation(s)
- Zhong-Hua Lu
- Department of Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Wei-Li Yu
- Department of Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Yun Sun
- Department of Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, Anhui Province, China
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Cappato S, Gamberale R, Bocciardi R, Brunelli S. Genetic and Acquired Heterotopic Ossification: A Translational Tale of Mice and Men. Biomedicines 2020; 8:biomedicines8120611. [PMID: 33327623 PMCID: PMC7765130 DOI: 10.3390/biomedicines8120611] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/10/2020] [Accepted: 12/13/2020] [Indexed: 12/11/2022] Open
Abstract
Heterotopic ossification is defined as an aberrant formation of bone in extraskeletal soft tissue, for which both genetic and acquired conditions are known. This pathologic process may occur in many different sites such as the skin, subcutaneous tissue, skeletal muscle and fibrous tissue adjacent to joints, ligaments, walls of blood vessels, mesentery and other. The clinical spectrum of this disorder is wide: lesions may range from small foci of ossification to massive deposits of bone throughout the body, typical of the progressive genetically determined conditions such as fibrodysplasia ossificans progressiva, to mention one of the most severe and disabling forms. The ectopic bone formation may be regarded as a failed tissue repair process in response to a variety of triggers and evolving towards bone formation through a multistage differentiation program, with several steps common to different clinical presentations and distinctive features. In this review, we aim at providing a comprehensive view of the genetic and acquired heterotopic ossification disorders by detailing the clinical and molecular features underlying the different human conditions in comparison with the corresponding, currently available mouse models.
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Affiliation(s)
- Serena Cappato
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Sciences (DINOGMI), University of Genova, 16132 Genova, Italy;
| | - Riccardo Gamberale
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Milano, Italy; (R.G.); (S.B.)
| | - Renata Bocciardi
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Sciences (DINOGMI), University of Genova, 16132 Genova, Italy;
- UOC Genetica Medica, IRCCS Giannina Gaslini, 16147 Genova, Italy
- Correspondence:
| | - Silvia Brunelli
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Milano, Italy; (R.G.); (S.B.)
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