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Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture

In an effort to identify therapeutic intervention strategies for the treatment of COVID-19, we have investigated a selection of FDA-approved small molecules and biologics that are commonly used to treat other human diseases. A investigation into 18 small molecules and 3 biologics was conducted in ce...

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Autores principales: Risner, Kenneth H., Tieu, Katie V., Wang, Yafei, Getz, Michael, Bakovic, Allison, Bhalla, Nishank, Nathan, Steven D., Conway, Daniel E., Macklin, Paul, Narayanan, Aarthi, Alem, Farhang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430595/
https://www.ncbi.nlm.nih.gov/pubmed/32817953
http://dx.doi.org/10.1101/2020.08.12.246389
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author Risner, Kenneth H.
Tieu, Katie V.
Wang, Yafei
Getz, Michael
Bakovic, Allison
Bhalla, Nishank
Nathan, Steven D.
Conway, Daniel E.
Macklin, Paul
Narayanan, Aarthi
Alem, Farhang
author_facet Risner, Kenneth H.
Tieu, Katie V.
Wang, Yafei
Getz, Michael
Bakovic, Allison
Bhalla, Nishank
Nathan, Steven D.
Conway, Daniel E.
Macklin, Paul
Narayanan, Aarthi
Alem, Farhang
author_sort Risner, Kenneth H.
collection PubMed
description In an effort to identify therapeutic intervention strategies for the treatment of COVID-19, we have investigated a selection of FDA-approved small molecules and biologics that are commonly used to treat other human diseases. A investigation into 18 small molecules and 3 biologics was conducted in cell culture and the impact of treatment on viral titer was quantified by plaque assay. The investigation identified 4 FDA-approved small molecules, Maraviroc, FTY720 (Fingolimod), Atorvastatin and Nitazoxanide that were able to inhibit SARS-CoV-2 infection. Confocal microscopy with over expressed S-protein demonstrated that Maraviroc reduced the extent of S-protein mediated cell fusion as observed by fewer multinucleate cells in the context of drug-treatment. Mathematical modeling of drug-dependent viral multiplication dynamics revealed that prolonged drug treatment will exert an exponential decrease in viral load in a multicellular/tissue environment. Taken together, the data demonstrate that Maraviroc, Fingolimod, Atorvastatin and Nitazoxanide inhibit SARS-CoV-2 in cell culture.
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spelling pubmed-74305952020-08-18 Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture Risner, Kenneth H. Tieu, Katie V. Wang, Yafei Getz, Michael Bakovic, Allison Bhalla, Nishank Nathan, Steven D. Conway, Daniel E. Macklin, Paul Narayanan, Aarthi Alem, Farhang bioRxiv Article In an effort to identify therapeutic intervention strategies for the treatment of COVID-19, we have investigated a selection of FDA-approved small molecules and biologics that are commonly used to treat other human diseases. A investigation into 18 small molecules and 3 biologics was conducted in cell culture and the impact of treatment on viral titer was quantified by plaque assay. The investigation identified 4 FDA-approved small molecules, Maraviroc, FTY720 (Fingolimod), Atorvastatin and Nitazoxanide that were able to inhibit SARS-CoV-2 infection. Confocal microscopy with over expressed S-protein demonstrated that Maraviroc reduced the extent of S-protein mediated cell fusion as observed by fewer multinucleate cells in the context of drug-treatment. Mathematical modeling of drug-dependent viral multiplication dynamics revealed that prolonged drug treatment will exert an exponential decrease in viral load in a multicellular/tissue environment. Taken together, the data demonstrate that Maraviroc, Fingolimod, Atorvastatin and Nitazoxanide inhibit SARS-CoV-2 in cell culture. Cold Spring Harbor Laboratory 2022-11-09 /pmc/articles/PMC7430595/ /pubmed/32817953 http://dx.doi.org/10.1101/2020.08.12.246389 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Risner, Kenneth H.
Tieu, Katie V.
Wang, Yafei
Getz, Michael
Bakovic, Allison
Bhalla, Nishank
Nathan, Steven D.
Conway, Daniel E.
Macklin, Paul
Narayanan, Aarthi
Alem, Farhang
Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture
title Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture
title_full Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture
title_fullStr Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture
title_full_unstemmed Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture
title_short Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture
title_sort maraviroc inhibits sars-cov-2 multiplication and s-protein mediated cell fusion in cell culture
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430595/
https://www.ncbi.nlm.nih.gov/pubmed/32817953
http://dx.doi.org/10.1101/2020.08.12.246389
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