Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro

Effective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian...

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Autores principales: Murray, Jackelyn, Hogan, Robert J., Martin, David E., Blahunka, Kathy, Sancilio, Fred D., Balyan, Rajiv, Lovern, Mark, Still, Richard, Tripp, Ralph A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433326/
https://www.ncbi.nlm.nih.gov/pubmed/34508172
http://dx.doi.org/10.1038/s41598-021-97658-w
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author Murray, Jackelyn
Hogan, Robert J.
Martin, David E.
Blahunka, Kathy
Sancilio, Fred D.
Balyan, Rajiv
Lovern, Mark
Still, Richard
Tripp, Ralph A.
author_facet Murray, Jackelyn
Hogan, Robert J.
Martin, David E.
Blahunka, Kathy
Sancilio, Fred D.
Balyan, Rajiv
Lovern, Mark
Still, Richard
Tripp, Ralph A.
author_sort Murray, Jackelyn
collection PubMed
description Effective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. Furthermore, we demonstrate that plasma concentrations up to 50-fold higher than the protein binding adjusted IC(90) value are achievable for 24 h following a single oral dose. These data support the potential clinical utility of probenecid to control SARS-CoV-2 infection in humans.
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spelling pubmed-84333262021-09-13 Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro Murray, Jackelyn Hogan, Robert J. Martin, David E. Blahunka, Kathy Sancilio, Fred D. Balyan, Rajiv Lovern, Mark Still, Richard Tripp, Ralph A. Sci Rep Article Effective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. Furthermore, we demonstrate that plasma concentrations up to 50-fold higher than the protein binding adjusted IC(90) value are achievable for 24 h following a single oral dose. These data support the potential clinical utility of probenecid to control SARS-CoV-2 infection in humans. Nature Publishing Group UK 2021-09-10 /pmc/articles/PMC8433326/ /pubmed/34508172 http://dx.doi.org/10.1038/s41598-021-97658-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Murray, Jackelyn
Hogan, Robert J.
Martin, David E.
Blahunka, Kathy
Sancilio, Fred D.
Balyan, Rajiv
Lovern, Mark
Still, Richard
Tripp, Ralph A.
Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro
title Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro
title_full Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro
title_fullStr Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro
title_full_unstemmed Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro
title_short Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro
title_sort probenecid inhibits sars-cov-2 replication in vivo and in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433326/
https://www.ncbi.nlm.nih.gov/pubmed/34508172
http://dx.doi.org/10.1038/s41598-021-97658-w
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