ArticleScientific reports2016
Natural HCV variants with increased replicative fitness due to NS3 helicase mutations in the C-terminal helix α18.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Hepatitis C virus NS3 helicase contributes to (-) strand RNA synthesis.Nature communications · 2025Article
- Article
- SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations.Pathogens (Basel, Switzerland) · 2022Article
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- Amino Acid Substitutions Associated with Treatment Failure for Hepatitis C Virus Infection.Journal of clinical microbiology · 2020Article
- Hepatitis C Virus Replication.Cold Spring Harbor perspectives in medicine · 2020Review
- Barrier-Independent, Fitness-Associated Differences in Sofosbuvir Efficacy against Hepatitis C Virus.Antimicrobial agents and chemotherapy · 2016Article
- Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High replicative fitness is a general determinant of a multidrug resistance phenotype and may explain lower sensitivity to direct-acting antiviral agents (DAAs) in some hepatitis C virus genotypes. Genetic diversity in the molecular target site of peptidomimetic NS3 protease inhibitors could impact variant replicative fitness and potentially add to virologic treatment failure. We selected NS3 helicase residues near the protease natural substrate in the NS3 domain interface and identified natural variants from a public database. Sequence diversity among different genotypes was identified and subsequently analyzed for potential effects of helicase variants on protein structure and function, and phenotypic effects on RNA replication and DAA resistance. We found increased replicative fitness in particular for amino acid substitutions at the NS3 helicase C-terminal helix α18. A network of strongly coupled residue pairs is identified. Helix α18 is part of this regulatory network and connects several NS3 functional elements involved in RNA replication. Among all genotypes we found distinct sequence diversity at helix α18 in particular for the most difficult-to-treat genotype 3. Our data suggest sequence diversity with implications for virus replicative fitness due to natural variants in helicase helix α18.
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Registered trials
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