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

ABSTRACT: 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 (EC₅₀). When V166L was introduced into a recombinant SARS-CoV-2 virus, a 1.5-fold increase in EC₅₀ was observed, indicating a high in vitro barrier to remdesivir resistance.

SUBMITTER: Checkmahomed L

PROVIDER: S-EPMC9295571 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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

Checkmahomed Liva L Carbonneau Julie J Du Pont Venice V Riola Nicholas C NC Perry Jason K JK Li Jiani J Paré Bastien B Simpson Shawn M SM Smith Martin A MA Porter Danielle P DP Boivin Guy G

Antimicrobial agents and chemotherapy 20220616 7

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 (EC50). When V166L was introduced into a recombinant SARS-CoV-2 virus, a 1.5-fold ...[more]

PMID: 35708323

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