Near-Neighbor Interactions in the NS3-4A Protease of HCV Impact Replicative Fitness of Drug-Resistant Viral Variants.

ABSTRACT: A variety of amino acid substitutions in the NS3-4A protease of the hepatitis C virus lead to protease inhibitor (PI) resistance. Many of these significantly impair the replication fitness of the resistant variants in a genotype- and subtype-dependent manner, a critical factor in determining the probability with which resistant variants will persist. However, the underlying molecular mechanisms are unknown. Here, we present a novel residue-interaction network approach to determine how near-neighbor interactions of PI resistance mutations in NS3-4A can impact protease functional sites dependent on their genomic background. We constructed subtype-specific consensus residue networks for subtypes 1a and 1b from protease structure ensembles combined with biological properties of protein residue

SUBMITTER: Doncheva NT 

PROVIDER: S-EPMC6554042 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature