RT Journal Article
SR Electronic
T1 The Effect of Famotidine on SARS-CoV-2 Proteases and Virus Replication
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.15.203059
DO 10.1101/2020.07.15.203059
A1 Madeline Loffredo
A1 Hector Lucero
A1 Da-Yuan Chen
A1 Aoife O’Connell
A1 Simon Bergqvist
A1 Ahmad Munawar
A1 Asanga Bandara
A1 Steff De Graef
A1 Stephen D. Weeks
A1 Florian Douam
A1 Mohsan Saeed
A1 Ali H. Munawar
YR 2020
UL http://biorxiv.org/content/early/2020/07/15/2020.07.15.203059.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.