Identification of a novel class of cyclic penta-peptides against hepatitis C virus as p7 channel blockers.

ABSTRACT: The hepatitis C virus (HCV) p7 viroporin protein is essential for viral assembly and release, suggesting its unrealised potential as a target for HCV interventions. Several classes of small molecules that can inhibit p7 through allosteric mechanisms have shown low efficacy. Here, we used a high throughput virtual screen to design a panel of eight novel cyclic penta-peptides (CPs) that target the p7 channel with high binding affinity. Further examination of the effects of these CPs in viral production assays indicated that CP7 exhibits the highest potency against HCV among them. Moreover, the IC₅₀ efficacy of CP7 in tests of strain Jc1-S282T suggested that this cyclopeptide could also effectively inhibit a drug-resistant HCV strain. A combination of nuclear magnetic resonance (NM

SUBMITTER: Wei S 

PROVIDER: S-EPMC9636413 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature