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Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential.
Kamyshnyi, Olexandr; Matskevych, Victoriya; Lenchuk, Tetyana; Strilbytska, Olha; Storey, Kenneth; Lushchak, Oleh.
  • Kamyshnyi O; Department of Microbiology, Virology and Immunology, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine.
  • Matskevych V; Department of Radiology and Radiation Medicine, Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine.
  • Lenchuk T; Department of Radiology and Radiation Medicine, Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine.
  • Strilbytska O; Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, Ivano-Frankivsk, Ukraine.
  • Storey K; Department of Biology, Carleton University, Ottawa, Canada.
  • Lushchak O; Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, Ivano-Frankivsk, Ukraine; Research and Development University, Ivano-Frankivsk, Ukraine. Electronic address: oleh.lushchak@pnu.edu.ua.
Biomed Pharmacother ; 144: 112230, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1517059
ABSTRACT
The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has become a serious challenge for medicine and science. Analysis of the molecular mechanisms associated with the clinical manifestations and severity of COVID-19 has identified several key points of immune dysregulation observed in SARS-CoV-2 infection. For diabetic patients, factors including higher binding affinity and virus penetration, decreased virus clearance and decreased T cell function, increased susceptibility to hyperinflammation, and cytokine storm may make these patients susceptible to a more severe course of COVID-19 disease. Metabolic changes induced by diabetes, especially hyperglycemia, can directly affect the immunometabolism of lymphocytes in part by affecting the activity of the mTOR protein kinase signaling pathway. High mTOR activity can enhance the progression of diabetes due to the activation of effector proinflammatory subpopulations of lymphocytes and, conversely, low activity promotes the differentiation of T-regulatory cells. Interestingly, metformin, an extensively used antidiabetic drug, inhibits mTOR by affecting the activity of AMPK. Therefore, activation of AMPK and/or inhibition of the mTOR-mediated signaling pathway may be an important new target for drug therapy in COVID-19 cases mostly by reducing the level of pro-inflammatory signaling and cytokine storm. These suggestions have been partially confirmed by several retrospective analyzes of patients with diabetes mellitus hospitalized for severe COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severity of Illness Index / Diabetes Mellitus / COVID-19 Drug Treatment / Hypoglycemic Agents / Immunity, Cellular / Metformin Type of study: Observational study / Prognostic study Limits: Humans Language: English Journal: Biomed Pharmacother Year: 2021 Document Type: Article Affiliation country: J.biopha.2021.112230

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severity of Illness Index / Diabetes Mellitus / COVID-19 Drug Treatment / Hypoglycemic Agents / Immunity, Cellular / Metformin Type of study: Observational study / Prognostic study Limits: Humans Language: English Journal: Biomed Pharmacother Year: 2021 Document Type: Article Affiliation country: J.biopha.2021.112230