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World J Virol. Mar 25, 2022; 11(2): 98-103
Published online Mar 25, 2022. doi: 10.5501/wjv.v11.i2.98
Too hard to die: Exercise training mediates specific and immediate SARS-CoV-2 protection
Konstantinos I Papadopoulos, Warachaya Sutheesophon, Tar-Choon Aw
Konstantinos I Papadopoulos, Research and Development, THAI StemLife, Bangkok 10310, Bangkok, Thailand
Warachaya Sutheesophon, Laboratory, THAI StemLife, Bangkok 10310, Bangkok, Thailand
Tar-Choon Aw, Laboratory Medicine, Changi General Hospital, Singapore 529889, Singapore, Singapore
Tar-Choon Aw, Department of Medicine, National University of Singapore, Singapore 119228, Singapore, Singapore
Author contributions: Papadopoulos KI had the original idea on the hypothesis concept and composed the manuscript; Sutheesophon W and Aw TC assisted in literature search, and all have made substantial, direct, and intellectual contributions to the work; all authors critically assessed the manuscript and approved it for publication.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Konstantinos I Papadopoulos, MD, PhD, Chairman, Chief Doctor, Research and Development, THAI StemLife, THAI StemLife, 566/3 Soi Ramkhamhaeng 39 (Thepleela 1), Prachaouthit Road, Wangthonglang, Bangkok 10310, Bangkok, Thailand. kostas@thaistemlife.co.th
Received: October 16, 2021
Peer-review started: October 16, 2021
First decision: December 16, 2021
Revised: December 19, 2021
Accepted: February 10, 2022
Article in press: February 10, 2022
Published online: March 25, 2022
Processing time: 156 Days and 21.3 Hours
Abstract

Several mechanisms may explain how exercise training mechanistically confers protection against coronavirus disease 2019 (COVID-19). Here we propose two new perspectives through which cardiorespiratory fitness may protect against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Physical exercise-activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling induces endothelial nitric oxide (NO) synthase (eNOS), increases NO bio-availability, and inhibits palmitoylation, leading to specific and immediate SARS-CoV-2 protection. AMPK signaling also induces angiotensin 1-7 release and enhances eNOS activation thus further mediating cardio- and reno-protection. Irisin, a myokine released from skeletal muscles during aerobic exercise, also participates in the AMPK/Akt-eNOS/NO pathway, protects mitochondrial functions in endothelial cells, and antagonizes renin angiotensin system proinflammatory action leading to reductions in genes associated with severe COVID-19 outcomes. Collectively, all the above findings point to the fact that increased AMPK and irisin activity through exercise training greatly benefits molecular processes that mediate specific, immediate, and delayed SARS-CoV-2 protection. Maintaining regular physical activity levels is a safe and affordable lifestyle strategy against the current and future pandemics and may also mitigate against obesity and cardiometabolic disease syndemics. Move more because a moving target is harder to kill.

Keywords: Adenosine monophosphate-activated protein kinase; Irisin; Physical exercise; Nitric oxide; Endothelial nitric oxide synthase; Severe acute respiratory syndrome coronavirus-2

Core Tip: Increased nitric oxide bio-availability through exercise training-induced activation of the master regulator of metabolism, the energy-sensing cellular enzyme adenosine monophosphate-activated protein kinase and irisin, the fat browning exercise hormone, released from skeletal muscles during aerobic exercise may mediate specific, immediate, and delayed severe acute respiratory syndrome coronavirus-2 protection. Move more because a moving target is harder to kill.