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Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2

BACKGROUND: Effective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection. METHODS: To evaluate the effe...

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Autores principales: Williamson, Brandi N., Feldmann, Friederike, Schwarz, Benjamin, Meade-White, Kimberly, Porter, Danielle P., Schulz, Jonathan, van Doremalen, Neeltje, Leighton, Ian, Kwe Yinda, Claude, Pérez-Pérez, Lizzette, Okumura, Atsushi, Lovaglio, Jamie, Hanley, Patrick W., Saturday, Greg, Bosio, Catharine M., Anzick, Sarah, Barbian, Kent, Cihlar, Tomas, Martens, Craig, Scott, Dana P., Munster, Vincent J., de Wit, Emmie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239049/
https://www.ncbi.nlm.nih.gov/pubmed/32511319
http://dx.doi.org/10.1101/2020.04.15.043166
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author Williamson, Brandi N.
Feldmann, Friederike
Schwarz, Benjamin
Meade-White, Kimberly
Porter, Danielle P.
Schulz, Jonathan
van Doremalen, Neeltje
Leighton, Ian
Kwe Yinda, Claude
Pérez-Pérez, Lizzette
Okumura, Atsushi
Lovaglio, Jamie
Hanley, Patrick W.
Saturday, Greg
Bosio, Catharine M.
Anzick, Sarah
Barbian, Kent
Cihlar, Tomas
Martens, Craig
Scott, Dana P.
Munster, Vincent J.
de Wit, Emmie
author_facet Williamson, Brandi N.
Feldmann, Friederike
Schwarz, Benjamin
Meade-White, Kimberly
Porter, Danielle P.
Schulz, Jonathan
van Doremalen, Neeltje
Leighton, Ian
Kwe Yinda, Claude
Pérez-Pérez, Lizzette
Okumura, Atsushi
Lovaglio, Jamie
Hanley, Patrick W.
Saturday, Greg
Bosio, Catharine M.
Anzick, Sarah
Barbian, Kent
Cihlar, Tomas
Martens, Craig
Scott, Dana P.
Munster, Vincent J.
de Wit, Emmie
author_sort Williamson, Brandi N.
collection PubMed
description BACKGROUND: Effective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection. METHODS: To evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy. RESULTS: In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue. CONCLUSIONS: Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia.
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spelling pubmed-72390492020-06-07 Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 Williamson, Brandi N. Feldmann, Friederike Schwarz, Benjamin Meade-White, Kimberly Porter, Danielle P. Schulz, Jonathan van Doremalen, Neeltje Leighton, Ian Kwe Yinda, Claude Pérez-Pérez, Lizzette Okumura, Atsushi Lovaglio, Jamie Hanley, Patrick W. Saturday, Greg Bosio, Catharine M. Anzick, Sarah Barbian, Kent Cihlar, Tomas Martens, Craig Scott, Dana P. Munster, Vincent J. de Wit, Emmie bioRxiv Article BACKGROUND: Effective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection. METHODS: To evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy. RESULTS: In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue. CONCLUSIONS: Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia. Cold Spring Harbor Laboratory 2020-04-22 /pmc/articles/PMC7239049/ /pubmed/32511319 http://dx.doi.org/10.1101/2020.04.15.043166 Text en https://creativecommons.org/publicdomain/zero/1.0/This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license (https://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Article
Williamson, Brandi N.
Feldmann, Friederike
Schwarz, Benjamin
Meade-White, Kimberly
Porter, Danielle P.
Schulz, Jonathan
van Doremalen, Neeltje
Leighton, Ian
Kwe Yinda, Claude
Pérez-Pérez, Lizzette
Okumura, Atsushi
Lovaglio, Jamie
Hanley, Patrick W.
Saturday, Greg
Bosio, Catharine M.
Anzick, Sarah
Barbian, Kent
Cihlar, Tomas
Martens, Craig
Scott, Dana P.
Munster, Vincent J.
de Wit, Emmie
Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
title Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
title_full Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
title_fullStr Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
title_full_unstemmed Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
title_short Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
title_sort clinical benefit of remdesivir in rhesus macaques infected with sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239049/
https://www.ncbi.nlm.nih.gov/pubmed/32511319
http://dx.doi.org/10.1101/2020.04.15.043166
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