The in-vitro effect of famotidine on SARS-CoV-2 proteases and virus replication

Abstract The lack of coronavirus-specific antiviral drugs has instigated multiple drug repurposing studies to redirect previously approved medicines for the treatment SARS-CoV-2, coronavirus behind ongoing COVID-19 pandemic. A recent, large-scale, retrospective clinical study showed that famotidine, when administered at a high dose hospitalized patients, reduced rates intubation and mortality. separate, patient-reported associated famotidine use with improvements in mild moderate symptoms such as cough shortness breath. While prospective, multi-center is ongoing, two parallel silico have proposed one SARS-CoV-2 proteases, 3CL pro or PL , potential molecular targets activity; however, this remains be experimentally validated. In report, we systematically analyzed effect on viral proteases virus replication. Leveraging series biophysical enzymatic assays, show neither binds nor inhibits functions . Similarly, no direct activity was observed concentrations up 200 µM, tested against different cell lines, including human line originating from lungs, primary target COVID-19. These results rule out direct-acting inhibitor replication warrant further investigation its mechanism action context