title: Hepatitis C virus translation inhibitors targeting the internal ribosomal entry site.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Dibrov
authors.forename: Jerod
authors.initials: J
authors.lastname: Parsons
authors.forename: Maia
authors.initials: M
authors.lastname: Carnevali
authors.forename: Shu
authors.initials: S
authors.lastname: Zhou
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Rynearson
authors.forename: Kejia
authors.initials: K
authors.lastname: Ding
authors.forename: Emily
authors.initials: E
authors.lastname: Garcia Sega
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Brunn
authors.forename: Mark A
authors.initials: MA
authors.lastname: Boerneke
authors.forename: Maria P
authors.initials: MP
authors.lastname: Castaldi
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermann
mesh_terms: D020121:5' Untranslated Regions; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D008958:Models, Molecular; D014176:Protein Biosynthesis / Q000187:drug effects*; D012270:Ribosomes / Q000187:drug effects*
chemical_list: D020121:5' Untranslated Regions