Affordable Access

deepdyve-link deepdyve-link
Publisher Website

Hepatitis C virus translation inhibitors targeting the internal ribosomal entry site.

Authors
Type
Published Article
Journal
Journal of Medicinal Chemistry
1520-4804
Publisher
American Chemical Society
Publication Date
Volume
57
Issue
5
Pages
1694–1707
Identifiers
DOI: 10.1021/jm401312n
PMID: 24138284
Source
Medline
License
Unknown

Abstract

The internal ribosome entry site (IRES) in the 5' untranslated region (UTR) of the hepatitis C virus (HCV) genome initiates translation of the viral polyprotein precursor. The unique structure and high sequence conservation of the 5' UTR render the IRES RNA a potential target for the development of selective viral translation inhibitors. Here, we provide an overview of approaches to block HCV IRES function by nucleic acid, peptide, and small molecule ligands. Emphasis will be given to the IRES subdomain IIa, which currently is the most advanced target for small molecule inhibitors of HCV translation. The subdomain IIa behaves as an RNA conformational switch. Selective ligands act as translation inhibitors by locking the conformation of the RNA switch. We review synthetic procedures for inhibitors as well as structural and functional studies of the subdomain IIa target and its ligand complexes.

Statistics

Seen <100 times