Anti-SARS-CoV-2 Action of Fluvoxamine may be Mediated by Endothelial Nitric Oxide Synthase

Comments on an article by M. Khosravi (see record 2022-40840-002), noting an additional mechanism that mechanistically supports fluvoxamine's (FLV) anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) properties. FLV-sigma-1 receptor (S1R) stimulation activates Akt-endothelial nitric oxide (NO) synthase (eNOS) signaling in the thoracic aorta while its vasculoprotective effect is nullified by co-administration of S1R antagonists, dramatically reducing eNOS and promoting atrial remodeling. Further, the replication of SARS-CoV has been found to be inhibited by NO through two clearly different mechanisms: (i) Decrease in the palmitoylation of nascently-expressed spike (S) protein that impacts the fusion of the S protein with its cognate receptor, angiotensin converting enzyme 2;(ii) Decline in the production of viral RNA in the very first stages of viral replication, most likely attributed to the impact on one or both of the cysteine proteases that are encoded in open reading frame 1a (Orf1a) protein of SARS-CoV. Patients with acute respiratory distress syndrome in a moderate-sized COVID-19 cohort showed lower soluble eNOS levels, implying that greater eNOS activity and the presumed increased NO synthesis probably prevent patients from serious lung complications. These findings could provide additional insights into new therapeutic applications of FLV in COVID-19. (PsycInfo Database Record (c) 2022 APA, all rights reserved)