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

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Antimicrob Agents Chemother


. 2022 Jun 16;e0019822.
doi: 10.1128/aac.00198-22. Online ahead of print.
In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance


Liva Checkmahomed ¹ , Julie Carbonneau ¹ , Venice Du Pont ² , Nicholas C Riola ² , Jason K Perry ² , Jiani Li ² , Bastien Paré ³ , Shawn M Simpson ³ , Martin A Smith ³ , Danielle P Porter ² , Guy Boivin ¹



Affiliations

• PMID: 35708323
• DOI: 10.1128/aac.00198-22

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.

Keywords: Nsp12 polymerase; SARS-CoV-2; remdesivir; resistance.