Natural HCV variants with increased replicative fitness due to NS3 helicase mutations in the C-terminal helix α18.

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 i

SUBMITTER: Stross C 

PROVIDER: S-EPMC4726148 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature