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小核糖核酸病毒抑制剂研究及WIN系列抗病毒化合物的发展

任龙, 焦宁*   

  1. 1. 北京大学医学部 天然药物及仿生药物国家重点实验室, 北京 100191
    2. 中国科学院 上海药物研究所 新药研究国家重点实验室, 上海 201203
  • 收稿日期:2012-09-10 修回日期:2012-09-30 出版日期:2012-10-25 发布日期:2012-10-25
  • 通讯作者: 焦宁*

A perspective on picornavirus inhibitors and concrete evolution of WIN compounds

Long Ren, Ning Jiao*   

  1. 1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China
    2. State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

  • Received:2012-09-10 Revised:2012-09-30 Online:2012-10-25 Published:2012-10-25
  • Contact: Ning Jiao*

摘要:

小核糖核酸病毒科是人类病毒性病原体中最大的家族之一。它可以导致一系列不同程度的临床症状, 从轻微的发热、普通感冒到严重的瘫痪型脊髓灰质炎、慢性阻塞性肺病等, 其中有一些极具致命性。小核糖核酸病毒还会引起动物性大流行, 给人类社会带来巨大的经济损失。虽然到目前为止, 还没有正式批准的能够有效预防或治疗小核糖核酸病毒感染的药物上市, 但是大量具有很好的抗小核糖核酸病毒活性的化合物已经被研发出来。通过对这些物质的研究, 也揭示出许多有关小核糖核酸病毒的信息。病毒信使RNA的翻译过程, 复制过程和病毒衣壳蛋白集中了这些被广泛研究的抗病毒物质的主要靶点。其中一类通过键合病毒衣壳, 抑制病毒吸附和脱壳的WIN系列化合物最为典型。因此本文将介绍抗小核糖核酸病毒化合物研究的总体概况并对WIN系列化合物的具体演进过程进行讨论。

关键词: 小核糖核酸病毒, 抗病毒物质, 衣壳键合抑制剂, WIN系列化合物, 普来可那立

Abstract: The family Picornaviridae is one of the largest families of human viral pathogens, causing an extensive range of clinical manifestations from mild fever, common cold to serious paralytic poliomyelitis, COPD, etc., some of which can even be life-threatening. Picornaviruses also cause zoonotic epidemics that result in dramatic social and economical losses. Although no efficient antivirus agent for prophylaxis or treatment of picornarivus infections has been officially approved yet, a large number of anti-picornavirus compounds with potent activity have been developed and investigated, through which further information about picornavirus has been revealed as well. Viral mRNA translation, viral mRNA replication and especially the viral capsid are the three main targets of these compounds having been extensively studied. The typical one is the WIN series of compounds that bind to the viral capsid and inhibit rival attachment or uncoating. Herein, a perspective on picornavirus inhibitors and a concrete evolution of WIN compounds will be presented in this paper.

Key words: Picornavirus, Antiviral agent, Capsid binding inhibitor, WIN compound, Pleconaril

中图分类号: 

Supporting:

Foundation items: National Basic Research Program of China (973 Program, Grant No. 2009CB825300), National Science Foundation of China (Grant No. 21172006).
*Corresponding author. Tel.: 86­010­82805297; Fax: 86­010­82805297