A Strategy for Evaluating Potential Antiviral Resistance to Small Molecule Drugs and Application to SARS-CoV-2

Overview

Journal Sci Rep

Specialty Science

Date 2023 Jan 10

PMID 36627366

Authors

Karen Sargsyan

Karine Mazmanian

Carmay Lim

Affiliations

Soon will be listed here.

Abstract

Alterations in viral fitness cannot be inferred from only mutagenesis studies of an isolated viral protein. To-date, no systematic analysis has been performed to identify mutations that improve virus fitness and reduce drug efficacy. We present a generic strategy to evaluate which viral mutations might diminish drug efficacy and applied it to assess how SARS-CoV-2 evolution may affect the efficacy of current approved/candidate small-molecule antivirals for M, PL, and RdRp. For each drug target, we determined the drug-interacting virus residues from available structures and the selection pressure of the virus residues from the SARS-CoV-2 genomes. This enabled the identification of promising drug target regions and small-molecule antivirals that the virus can develop resistance. Our strategy of utilizing sequence and structural information from genomic sequence and protein structure databanks can rapidly assess the fitness of any emerging virus variants and can aid antiviral drug design for future pathogens.

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