In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance

In vitro selection of remdesivir-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the emergence of a V166L substitution, located outside of the polymerase active site of the Nsp12 protein, after 9 passages of a single lineage. V166L remained the only Nsp12 substitution...

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Autores principales: Checkmahomed, Liva, Carbonneau, Julie, Du Pont, Venice, Riola, Nicholas C., Perry, Jason K., Li, Jiani, Paré, Bastien, Simpson, Shawn M., Smith, Martin A., Porter, Danielle P., Boivin, Guy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Antiviral Agents
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295571/
https://www.ncbi.nlm.nih.gov/pubmed/35708323
http://dx.doi.org/10.1128/aac.00198-22
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author Checkmahomed, Liva
Carbonneau, Julie
Du Pont, Venice
Riola, Nicholas C.
Perry, Jason K.
Li, Jiani
Paré, Bastien
Simpson, Shawn M.
Smith, Martin A.
Porter, Danielle P.
Boivin, Guy
author_facet Checkmahomed, Liva
Carbonneau, Julie
Du Pont, Venice
Riola, Nicholas C.
Perry, Jason K.
Li, Jiani
Paré, Bastien
Simpson, Shawn M.
Smith, Martin A.
Porter, Danielle P.
Boivin, Guy
author_sort Checkmahomed, Liva
collection PubMed
description In vitro selection of remdesivir-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the emergence of a V166L substitution, located outside of the polymerase active site of the Nsp12 protein, after 9 passages of a single lineage. V166L remained the only Nsp12 substitution after 17 passages (10 μM remdesivir), conferring a 2.3-fold increase in 50% effective concentration (EC(50)). When V166L was introduced into a recombinant SARS-CoV-2 virus, a 1.5-fold increase in EC(50) was observed, indicating a high in vitro barrier to remdesivir resistance.
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spelling pubmed-92955712022-07-20 In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance Checkmahomed, Liva Carbonneau, Julie Du Pont, Venice Riola, Nicholas C. Perry, Jason K. Li, Jiani Paré, Bastien Simpson, Shawn M. Smith, Martin A. Porter, Danielle P. Boivin, Guy Antimicrob Agents Chemother Antiviral Agents In vitro selection of remdesivir-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the emergence of a V166L substitution, located outside of the polymerase active site of the Nsp12 protein, after 9 passages of a single lineage. V166L remained the only Nsp12 substitution after 17 passages (10 μM remdesivir), conferring a 2.3-fold increase in 50% effective concentration (EC(50)). When V166L was introduced into a recombinant SARS-CoV-2 virus, a 1.5-fold increase in EC(50) was observed, indicating a high in vitro barrier to remdesivir resistance. American Society for Microbiology 2022-06-16 /pmc/articles/PMC9295571/ /pubmed/35708323 http://dx.doi.org/10.1128/aac.00198-22 Text en Copyright © 2022 American Society for Microbiology. https://doi.org/10.1128/ASMCopyrightv2All Rights Reserved (https://doi.org/10.1128/ASMCopyrightv2) . https://doi.org/10.1128/ASMCopyrightv2This article is made available via the PMC Open Access Subset for unrestricted noncommercial re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Antiviral Agents
Checkmahomed, Liva
Carbonneau, Julie
Du Pont, Venice
Riola, Nicholas C.
Perry, Jason K.
Li, Jiani
Paré, Bastien
Simpson, Shawn M.
Smith, Martin A.
Porter, Danielle P.
Boivin, Guy
In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
title In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
title_full In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
title_fullStr In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
title_full_unstemmed In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
title_short In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
title_sort in vitro selection of remdesivir-resistant sars-cov-2 demonstrates high barrier to resistance
topic Antiviral Agents
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295571/
https://www.ncbi.nlm.nih.gov/pubmed/35708323
http://dx.doi.org/10.1128/aac.00198-22
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