tetano
Editor, Senior Moderator
Sci Rep
. 2021 Mar 8;11(1):5433.
doi: 10.1038/s41598-021-84782-w.
The in-vitro effect of famotidine on sars-cov-2 proteases and virus replication
Madeline Loffredo[SUP] 1 2 [/SUP], Hector Lucero[SUP] 1 2 [/SUP], Da-Yuan Chen[SUP] 3 4 [/SUP], Aoife O'Connell[SUP] 3 5 [/SUP], Simon Bergqvist[SUP] 6 [/SUP], Ahmad Munawar[SUP] 1 2 [/SUP], Asanga Bandara[SUP] 1 2 [/SUP], Steff De Graef[SUP] 1 7 [/SUP], Stephen D Weeks[SUP] 1 7 [/SUP], Florian Douam[SUP] 3 5 [/SUP], Mohsan Saeed[SUP] 8 9 [/SUP], Ali H Munawar[SUP] 10 11 12 [/SUP]
Affiliations
Abstract
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, 3CL[SUP]pro[/SUP] or PL[SUP]pro[/SUP], 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 3CL[SUP]pro[/SUP] and PL[SUP]pro[/SUP]. Similarly, no direct antiviral activity of famotidine was observed at concentrations of up to 200 ?M, 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.
. 2021 Mar 8;11(1):5433.
doi: 10.1038/s41598-021-84782-w.
The in-vitro effect of famotidine on sars-cov-2 proteases and virus replication
Madeline Loffredo[SUP] 1 2 [/SUP], Hector Lucero[SUP] 1 2 [/SUP], Da-Yuan Chen[SUP] 3 4 [/SUP], Aoife O'Connell[SUP] 3 5 [/SUP], Simon Bergqvist[SUP] 6 [/SUP], Ahmad Munawar[SUP] 1 2 [/SUP], Asanga Bandara[SUP] 1 2 [/SUP], Steff De Graef[SUP] 1 7 [/SUP], Stephen D Weeks[SUP] 1 7 [/SUP], Florian Douam[SUP] 3 5 [/SUP], Mohsan Saeed[SUP] 8 9 [/SUP], Ali H Munawar[SUP] 10 11 12 [/SUP]
Affiliations
- PMID: 33686143
- DOI: 10.1038/s41598-021-84782-w
Abstract
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, 3CL[SUP]pro[/SUP] or PL[SUP]pro[/SUP], 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 3CL[SUP]pro[/SUP] and PL[SUP]pro[/SUP]. Similarly, no direct antiviral activity of famotidine was observed at concentrations of up to 200 ?M, 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.