title: Recent advances in discovery and development of promising therapeutics against hepatitis C virus NS5B RNA-dependent RNA polymerase.
abstract: Lack of highly effective and safe therapeutics for hepatitis C virus (HCV) infection provides an opportunity as well as a challenge to discover novel and potent anti-HCV drugs. HCV NS5B RNA-dependent RNA polymerase (RdRp) is responsible for viral genome replication and thus constitutes a valid target for therapeutic intervention. To date, numerous HCV NS5B RdRp inhibitors have been discovered. This review focuses on the recent advances in discovery, mechanism of action studies and biological characterization of several distinct classes of potent inhibitors for NS5B RdRp. The clinical efficacy and developmental status of several promising compounds are also outlined.
authors.affiliation: Drug Discovery, Valeant Pharmaceutical International, 3300 Hyland Avenue, Costa Mesa, CA 92626, USA. jwu@valeant.com
authors.forename: Jim Zhen
authors.initials: JZ
authors.lastname: Wu
authors.forename: Nanhua
authors.initials: N
authors.lastname: Yao
authors.forename: Michelle
authors.initials: M
authors.lastname: Walker
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D016679:Genome, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D011485:Protein Binding; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase