title: Replicon cell culture system as a valuable tool in antiviral drug discovery against hepatitis C virus.
abstract: Discovery of potential therapeutics against hepatitis C virus (HCV) infection has been hampered in the past decade by the inability to grow this virus in tissue culture and by the lack of robust small animal models. This situation has been improved by the recent development of a selectable HCV replicon cell culture system. For the first time, drug discovery scientists are able to screen large compound collections using the replicon cell culture system to identify small molecules with the potential to inhibit HCV RNA replication. The replicon system has also been used to elucidate inhibitors' antiviral mechanism of action and to optimize antiviral potency. In this review, we will summarize the recent development of HCV replicon cell culture system and its use in anti-HCV drug discovery. The antiviral activities of promising lead compounds are also reviewed.
authors.affiliation: Drug Discovery, Valeant Pharmaceuticals International, Costa Mesa, CA, USA.
authors.forename: Nigel
authors.initials: N
authors.lastname: Horscroft
authors.forename: Vicky C H
authors.initials: VC
authors.lastname: Lai
authors.forename: Wayne
authors.initials: W
authors.lastname: Cheney
authors.forename: Nanhua
authors.initials: N
authors.lastname: Yao
authors.forename: Jim Z
authors.initials: JZ
authors.lastname: Wu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhong
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D012093:Replicon / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014776:Virus Cultivation / Q000379:methods; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D012324:RNA-Dependent RNA Polymerase