Probing of exosites leads to novel inhibitor scaffolds of HCV NS3/4A proteinase.

ABSTRACT:

Background

Hepatitis C is a treatment-resistant disease affecting millions of people worldwide. The hepatitis C virus (HCV) genome is a single-stranded RNA molecule. After infection of the host cell, viral RNA is translated into a polyprotein that is cleaved by host and viral proteinases into functional, structural and non-structural, viral proteins. Cleavage of the polyprotein involves the viral NS3/4A proteinase, a proven drug target. HCV mutates as it replicates and, as a result, multiple emerging quasispecies become rapidly resistant to anti-virals, including NS3/4A inhibitors.

Methodology/principal findings

To circumvent drug resistance and complement the existing anti-virals, NS3/4A inhibitors, which are additional and distinct from the FDA-approved telaprevir and boce

SUBMITTER: Shiryaev SA 

PROVIDER: S-EPMC3388044 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature