AI Article Synopsis
- Alterations in viral fitness can't simply be determined by studying mutated viral proteins in isolation; a broader approach is needed.
- The authors propose a strategy to evaluate viral mutations that may reduce the effectiveness of current antiviral drugs, specifically for SARS-CoV-2.
- By analyzing viral genome sequences and protein structures, they identify regions where mutations could lead to drug resistance, potentially assisting in the development of new antiviral therapies.
Article 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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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9831016 | PMC |
| http://dx.doi.org/10.1038/s41598-023-27649-6 | DOI Listing |
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