Discovery of New Inhibitors of Hepatitis C Virus NS3/4A Protease and Its D168A Mutant.

ABSTRACT: Hepatitis C virus (HCV) is a human pathogen with high morbidity. The HCV NS3/4A protease is essential for viral replication and is one of the top three drug targets. Several drugs targeting the protease have been developed, but drug-resistant mutant strains emerged. Here, we screened a library and synthesized a novel class of small molecules based on a tryptophan derivative scaffold identified as HCV NS3/4A protease inhibitors that are active against both wild type and mutant form of the protease. Only the compounds with predicted binding poses not affected by the most frequent mutations in the active site were selected for experimental validation. The antiviral activities were evaluated by replicon and enzymatic assays. Twenty-two compounds were found to inhibit HCV with EC₅₀ v

SUBMITTER: Meewan I 

PROVIDER: S-EPMC6796237 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature