Wang Q M
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Prog Drug Res. 1999;52:197-219. doi: 10.1007/978-3-0348-8730-4_5.
The picornavirus family contains several human pathogens including human rhinovirus (HRV) and hepatitis A virus (HAV). In the case of HRVs, these small single-stranded positive-sense RNA viruses translate their genetic information into a polyprotein precursor which is further processed mainly by two viral proteases designated 2A and 3C. The 2A protease (2Apro) makes the first cleavage between the structural and non-structural proteins, while 3C protease (3Cpro) catalyzes most of the remaining internal cleavages. It has been shown that both 2Apro and 3Cpro are cysteine proteases but their overall protein folding is more like trypsin-type serine proteases. Due to their unique protein structure and essential roles in viral replication, 2Apro and 3Cpro have been viewed as excellent targets for antiviral intervention. In recent years, considerable efforts have been made in the development of antiviral compounds targeting these proteases. This article summarizes the recent approaches in the design of novel 2A and 3C protease inhibitors as potential antiviral agents for the treatment of picornaviral infections.
小核糖核酸病毒科包含几种人类病原体，包括人鼻病毒（HRV）和甲型肝炎病毒（HAV）。就人鼻病毒而言，这些小型单链正链RNA病毒将其遗传信息翻译成一种多蛋白前体，该前体主要由两种名为2A和3C的病毒蛋白酶进一步加工。2A蛋白酶（2Apro）在结构蛋白和非结构蛋白之间进行首次切割，而3C蛋白酶（3Cpro）催化其余大部分内部切割。已表明2Apro和3Cpro都是半胱氨酸蛋白酶，但其整体蛋白质折叠更像胰蛋白酶型丝氨酸蛋白酶。由于其独特的蛋白质结构以及在病毒复制中的重要作用，2Apro和3Cpro被视为抗病毒干预的理想靶点。近年来，在开发针对这些蛋白酶的抗病毒化合物方面已付出了相当大的努力。本文总结了设计新型2A和3C蛋白酶抑制剂作为治疗小核糖核酸病毒感染的潜在抗病毒药物的最新方法。
