The effect of famotidine on sars-cov-2 proteases and virus replication in-vitro

Key Messages

In contrast to the findings of other researchers, this laboratory study reports a series of cellular experiments that indicate famotidine cannot inhibit the SARS-CoV-2 proteases, PLpro and 3CLpro.

Furthermore, the authors could not show any direct antiviral activity by famotidine.

They propose that additional research is required to determine the underlying mechanism of action famotidine in treating COVID-19.

Scientific Reports

Publication Date: March 8, 2021
Peer Reviewed: Yes
Publication Type: Original | Preclinical

The in-vitro effect of famotidine on sars-cov-2 proteases and virus replication

Madeline Loffredo, Hector Lucero, Da-Yuan Chen, Aoife O’Connell, Simon Bergqvist, Ahmad Munawar, Asanga Bandara, Steff De Graef, Stephen D. Weeks, Florian Douam, Mohsan Saeed, Ali H. Munawar


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