Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential

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...

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Autores principales:	Olexandr Kamyshnyi, Victoriya Matskevych, Tetyana Lenchuk, Olha Strilbytska, Kenneth Storey, Oleh Lushchak
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	COVID-19 Immunometabolism Lymphocytes Metformin Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/1d8b5f4dd35445109b1f2f3646cdef92
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spelling	oai:doaj.org-article:1d8b5f4dd35445109b1f2f3646cdef922021-11-14T04:28:42ZMetformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential0753-332210.1016/j.biopha.2021.112230https://doaj.org/article/1d8b5f4dd35445109b1f2f3646cdef922021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221010143https://doaj.org/toc/0753-3322The 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.Olexandr KamyshnyiVictoriya MatskevychTetyana LenchukOlha StrilbytskaKenneth StoreyOleh LushchakElsevierarticleCOVID-19ImmunometabolismLymphocytesMetforminTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112230- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 Immunometabolism Lymphocytes Metformin Therapeutics. Pharmacology RM1-950
spellingShingle	COVID-19 Immunometabolism Lymphocytes Metformin Therapeutics. Pharmacology RM1-950 Olexandr Kamyshnyi Victoriya Matskevych Tetyana Lenchuk Olha Strilbytska Kenneth Storey Oleh Lushchak Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential
description	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.
format	article
author	Olexandr Kamyshnyi Victoriya Matskevych Tetyana Lenchuk Olha Strilbytska Kenneth Storey Oleh Lushchak
author_facet	Olexandr Kamyshnyi Victoriya Matskevych Tetyana Lenchuk Olha Strilbytska Kenneth Storey Oleh Lushchak
author_sort	Olexandr Kamyshnyi
title	Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential
title_short	Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential
title_full	Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential
title_fullStr	Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential
title_full_unstemmed	Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential
title_sort	metformin to decrease covid-19 severity and mortality: molecular mechanisms and therapeutic potential
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/1d8b5f4dd35445109b1f2f3646cdef92
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Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential

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