Structure of the HCV Internal Ribosome Entry Site Subdomain IIa RNA in Complex with a Viral Translation Inhibitor

Abstract

The internal ribosome entry site (IRES) in the 5' untranslated region (UTR) of the hepatitis C virus (HCV) RNA genome is responsible for initiation of viral protein synthesis. The IRES RNA contains autonomously folding domains that are potential targets for antiviral translation inhibitors. Here, we describe the experimental crystal structure determination of the IRES subdomain IIa in complex with a previously discovered benzimidazole translation inhibitor. The structure of an inhibitor complex of the highly conserved IRES subdomain IIa holds promise for structure-based design of new anti-HCV drugs.