title: Identification of novel small molecules as inhibitors of hepatitis C virus by structure-based virtual screening.
abstract: Hepatitis C virus (HCV) NS3/NS4A serine protease is essential for viral replication, which is regarded as a promising drug target for developing direct-acting anti-HCV agents. In this study, sixteen novel compounds with cell-based HCV replicon activity ranging from 3.0 to 28.2 μM (IC50) were successfully identified by means of structure-based virtual screening. Compound 5 and compound 11, with an IC50 of 3.0 μM and 5.1 μM, respectively, are the two most potent molecules with low cytotoxicity.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. myzheng@mail.shcnc.ac.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhou
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Luo
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zheng
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Kaixian
authors.initials: K
authors.lastname: Chen
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry*; D016174:Hepacivirus / Q000737:chemistry / Q000187:drug effects* / Q000472:pathogenicity; D006526:Hepatitis C / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D011487:Protein Conformation / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry; D014584:User-Computer Interface; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D054852:Small Molecule Libraries; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases