Identification of novel small molecules as inhibitors of hepatitis C virus by structure-based virtual screening

Jing Li; Xian Liu; Shanshan Li; Yulan Wang; Nannan Zhou; Cheng Luo; Xiaomin Luo; Mingyue Zheng; Hualiang Jiang; Kaixian Chen

doi:10.3390/ijms141122845

Identification of novel small molecules as inhibitors of hepatitis C virus by structure-based virtual screening

Int J Mol Sci. 2013 Nov 20;14(11):22845-56. doi: 10.3390/ijms141122845.

Authors

Jing Li¹, Xian Liu, Shanshan Li, Yulan Wang, Nannan Zhou, Cheng Luo, Xiaomin Luo, Mingyue Zheng, Hualiang Jiang, Kaixian Chen

Affiliation

¹ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / administration & dosage
Antiviral Agents / chemistry*
Hepacivirus / chemistry
Hepacivirus / drug effects*
Hepacivirus / pathogenicity
Hepatitis C / drug therapy*
Hepatitis C / pathology
Hepatitis C / virology
Humans
Protein Conformation / drug effects
Small Molecule Libraries / chemistry
User-Computer Interface
Viral Nonstructural Proteins / antagonists & inhibitors
Viral Nonstructural Proteins / chemistry*

Substances

Antiviral Agents
NS3 protein, hepatitis C virus
Small Molecule Libraries
Viral Nonstructural Proteins