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 of SARS-CoV-2, the coronavirus behind the ongoing COVID-19 pandemic. A recent, large-scale, retrospective clinical study showed that...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/e07d8710ce004328ab2ec83a48a74f35 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:e07d8710ce004328ab2ec83a48a74f35 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:e07d8710ce004328ab2ec83a48a74f352021-12-02T13:30:11ZThe in-vitro effect of famotidine on sars-cov-2 proteases and virus replication10.1038/s41598-021-84782-w2045-2322https://doaj.org/article/e07d8710ce004328ab2ec83a48a74f352021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84782-whttps://doaj.org/toc/2045-2322Abstract 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.Madeline LoffredoHector LuceroDa-Yuan ChenAoife O’ConnellSimon BergqvistAhmad MunawarAsanga BandaraSteff De GraefStephen D. WeeksFlorian DouamMohsan SaeedAli H. MunawarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q 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 in-vitro effect of famotidine on sars-cov-2 proteases and virus replication |
| description |
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, 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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Madeline Loffredo |
| title |
The in-vitro effect of famotidine on sars-cov-2 proteases and virus replication |
| title_short |
The in-vitro effect of famotidine on sars-cov-2 proteases and virus replication |
| title_full |
The in-vitro effect of famotidine on sars-cov-2 proteases and virus replication |
| title_fullStr |
The in-vitro effect of famotidine on sars-cov-2 proteases and virus replication |
| title_full_unstemmed |
The in-vitro effect of famotidine on sars-cov-2 proteases and virus replication |
| title_sort |
in-vitro effect of famotidine on sars-cov-2 proteases and virus replication |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/e07d8710ce004328ab2ec83a48a74f35 |
| work_keys_str_mv |
AT madelineloffredo theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT hectorlucero theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT dayuanchen theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT aoifeoconnell theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT simonbergqvist theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT ahmadmunawar theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT asangabandara theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT steffdegraef theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT stephendweeks theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT floriandouam theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT mohsansaeed theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT alihmunawar theinvitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT madelineloffredo invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT hectorlucero invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT dayuanchen invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT aoifeoconnell invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT simonbergqvist invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT ahmadmunawar invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT asangabandara invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT steffdegraef invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT stephendweeks invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT floriandouam invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT mohsansaeed invitroeffectoffamotidineonsarscov2proteasesandvirusreplication AT alihmunawar invitroeffectoffamotidineonsarscov2proteasesandvirusreplication |
| _version_ |
1718392946160566272 |