<i>In Vitro</i> Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
Liva Checkmahomed, Julie Carbonneau, Venice Du Pont, Nicholas C. Riola, Jason K. Perry, Jiani Li, Bastien Paré, Shawn M. Simpson, Martin A. Smith, Danielle Porter, Guy Boivin
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 (EC 50 ).
Topics & Concepts
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)In vitro2019-20 coronavirus outbreakVirologySelection (genetic algorithm)BetacoronavirusMicrobiologyDrug resistanceResistance (ecology)ChemistryBiologyMedicineGeneticsComputer scienceOutbreakInfectious disease (medical specialty)EcologyDiseaseArtificial intelligencePathologySARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesSARS-CoV-2 detection and testing