COVID-19 and L-arginine Supplementations:Yet to Find the Missed Key

摘要

Current coronavirus disease(COVID-19) is regarded as a primary respiratory and vascular disease leading to acute lung injury(ALI),acute respiratory distress syndrome(ARDS),and endothelial dysfunction(ED) in severe cases.The causative virus of COVID-19 is SARS-CoV-2,which binds angiotensin-converting enzyme 2(ACE2) for its entry.It has been shown that ED is linked to various COVID-19 complications since endothelial cells are regarded as the chief barrier against SARS-CoV-2 invasion.SARS-CoV-2-indued ED leads to endotheliitis and thrombosis due to endothelial nitric oxide(NO) inhibition with subsequent vasoconstriction and tissue hypoxia.Loss of vasodilator NO and anti-thrombin factor from endothelial SARS-CoV-2 infection contribute to the progression of vascular dysfunction and coagulopathy.Therefore,NO restoration improves pulmonary function and hinders viral replication during respiratory viral infections,including COVID-19.L-arginine is a sem-iessential amino acid that has antiviral and immunomodulatory effects as well as improves the biosynthesis of NO in endothelial cells.L-arginine may reduce the risk of ALI through inhibition of generation of peroxynitrite and suppression of the release of proinflammatory cytokines from alveolar macrophages.Of interest,restoration of NO by L-arginine may attenuate SARS-CoV-2 infection through different mechanisms,including reduction binding of SARS-CoV-2 to ACE2,inhibition of transmembrane protease serine-type 2(TMPR552),critical for the activation of SARS-CoV-2 spike protein and cellular entry,inhibition proliferation and replication of SARS-CoV-2,and prevention of SARS-CoV-2-induced coagulopathy.In conclusion,through antiviral and immunomodulatory effects,L-arginine and released NO have mutual and interrelated actions against SARS-CoV-2 infection.