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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Detalles Bibliográficos
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
Descripción
Sumario: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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