Rapid resistance profiling of SARS-CoV-2 protease inhibitors
Seyed Arad Moghadasi, Rayhan G. Biswas, Daniel A. Harki, Reuben S. Harris
Abstract
Abstract Resistance to nirmatrelvir (Paxlovid) has been shown by multiple groups and may already exist in clinical SARS-CoV-2 isolates. Here a robust cell-based assay is used to determine the relative potencies of nirmatrelvir, ensitrelvir, and FB2001 against a panel of SARS-CoV-2 main protease (M pro ) variants. The results reveal that these three drugs have at least partly distinct resistance mutation profiles and raise the possibility that the latter compounds may be effective in some instances of Paxlovid resistance and vice versa .
Topics & Concepts
ProteaseSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)VirologyCoronavirus disease 2019 (COVID-19)2019-20 coronavirus outbreakBiologyProfiling (computer programming)Drug resistanceComputational biologyGeneticsMedicineEnzymeComputer scienceInfectious disease (medical specialty)BiochemistryDiseasePathologyOutbreakOperating systemSARS-CoV-2 and COVID-19 ResearchComputational Drug Discovery Methodsvaccines and immunoinformatics approaches