【摘要】 随着近年来高致病性禽流感疫情的出现,历史上曾给人类生命造成严重威胁的大流感有可能再次大面积流行,这引起了世界范围内的普遍关注。作为合理药物设计一个成功范例的抗流感药物达菲,对患禽流感的病人的治疗也有效。它是一个流感病毒唾液酸苷酶抑制剂,可以对病毒感染细胞过程中关键的释放和扩散步骤进行阻断。这一事件促使人们对抗流感药物的研发产生了极大的兴趣。本文在简述唾液酸苷酶功能、催化反应机理的基础上,对近年来流感病毒唾液酸苷酶抑制剂的研究状况进行综述,重点介绍基于过渡态的药物设计、合成糖模拟物的结构骨架类型以及构效关系研究。由于唾液酸苷酶也与许多其它疾病的发生和发展过程密切相关,不同来源的唾液酸苷酶在结构上具有一些共同的特征,因此有关流感病毒唾液酸苷酶抑制剂的研发知识和经验也必将对其它疾病的唾液酸苷酶抑制剂的研究有直接的帮助。更多还原

【Abstract】 Due to the recent emergence of avian flu,the possibility of a pandemic wave of life-threatening flu is a serious worldwide concern.Tamiflu,one of the outstanding successes of rational drug design,becomes a star drug that inhibits virus sialidase(neuraminidase),an enzyme crucial for the release and spread of the influenza virus from infected cells.This event stimulated many people to seek a share of the potentially huge flu drug market.On the basis of a brief introduction of sialidases and their functions,this review summarizes the recent advances in influenza virus sialidase inhibitors with particular focus on the transition state-based design,the synthetic scaffold types of carbohydrate mimetics,and the structure-activity relationships of structure-based sialidase inhibitors.Since sialidases are involved in the pathogenesis of a wide range of other diseases,the knowledge and expertise gained from the influenza study could be used in the design of other drugs,given that they all share certain structural features.更多还原