Epoxide based inhibitors of the hepatitis C virus non-structural 2 autoprotease

被引：5
作者：
Shaw, Joseph [1 ,2 ,3 ]
Fishwick, Colin W. G. [2 ,3 ]
Harris, Mark [1 ,3 ]
机构：
[1] Univ Leeds, Fac Biol Sci, Sch Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England
[2] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England
[3] Univ Leeds, Astbuty Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England
来源：
ANTIVIRAL RESEARCH | 2015年 / 117卷
基金：
英国工程与自然科学研究理事会; 英国惠康基金;
关键词：
Hepatitis C virus; NS2; Inhibitor; Autoprotease; Epoxide; IN-VITRO; PROTEASE; REPLICATION; SERINE; NS2;
D O I：
10.1016/j.antiviral.2015.02.005
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Hepatitis C virus (HCV) non-structural 2 (NS2) encodes an essential protease activity responsible for processing at the NS2-NS3 junction which represents an attractive antiviral target Attempts to inhibit the NS2 autoprotease with mechanism-based protease inhibitors and substrate peptides have had limited success. We report a series of epoxide-containing small molecules capable of blocking NS2-NS3 proteolysis in vitro and demonstrate the potential for selectivity towards the NS2 autoprotease. A compound within this series was able to perturb HCV genome replication in a subgenomic replicon system only when polyprotein processing was dependent on NS2 autoprotease activity, in addition it inhibited replication of full length HCV. These findings suggest blocking HCV polyprotein processing through inhibition of the NS2 autoprotease represents a viable route to exert an antiviral effect. (C) 2015 The Authors. Published by Elsevier B.V.
引用
收藏
页码：20 / 26
页数：7
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