A strategy for evaluating potential antiviral resistance to small molecule drugs and application to SARS-CoV-2.
Sci Rep
; 13(1): 502, 2023 01 10.
Article
in English
| MEDLINE | ID: covidwho-2186079
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 Mpro, PLpro, 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Drug Resistance, Viral
/
SARS-CoV-2
Type of study:
Experimental Studies
/
Systematic review/Meta Analysis
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Sci Rep
Year:
2023
Document Type:
Article
Affiliation country:
S41598-023-27649-6
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