病毒跨膜蛋白的结构功能与抗病毒药物设计-微生物与感染-复旦大学.PDF

微生物 与感染 2009 年 12 月第 4 卷第 4 期 Journal of Microbes and Infection, December 2009, Vol. 4, No. 4 ·23 1 · ·综 述 · 病毒跨膜蛋 白的结构功能与抗病毒药物设计 杨金华, 叶荣 复旦大学上海医学院, 上海 200032 摘 要: 根据病毒衣壳表面有无包膜结构, 病毒可被分为无包膜病毒和有包膜病毒。包膜病毒的膜蛋白在病 毒的吸附、侵入、脱壳、生物大分子合成、病毒颗粒的装配与释放等生命周期中起重要作用。某些包膜病毒的 膜蛋白对病毒侵入宿主细胞的膜融合是不可或缺的。结构分析显示, Ⅰ型和 Ⅱ型病毒融合蛋白采用类似的膜 融合方式。此外, 流行性感冒病毒的M2 蛋白、人类免疫缺陷病毒 1 型( HIV- 1) 的 Vpu 蛋白、严重急性呼吸综 合征冠状病毒( SARS-CoV) 3a 蛋白等膜蛋白还具有离子通道功能。针对这些病毒膜融合蛋 白设计的抑制分 子, 将为研发抗包膜病毒新型药物提供新思路和策略。本文以3 种病毒膜融合蛋白为例, 对其融合机制、跨膜 蛋白离子通道功能及其在抗病毒药物设计中的应用作一简要综述。 关键词: 病毒跨膜蛋白; 膜融合; 病毒性离子通道; 药靶 Advances in the viral transmembrane proteins: structure, function and antiviral drug design YANG Jin-Hua, YE Rong Shanghai Medical College, Fudan University, Shanghai 200032, China Abstract: Viruses have been classified into enveloped and non-enveloped subtypes according to their surface structures. The membrane proteins of the enveloped viruses are involved in the attachment, penetration, uncoating, replication, and release of the viruses. The special membrane proteins are essential for the membrane fusion by which the enveloped viruses penetrate into host cells. Furthermore, structural data show that class I and class II viral fusion proteins utilize a similar principle in membrane fusion. In addition, there are some viral membrane proteins, such as M2 of the influenza virus, Vpu of the human immunodeficiency virus type 1 ( HIV- 1) , 3a of the severe acute respiratory syndrome coronavirus ( SARS-CoV) , among others, that have ion channel functions. The processes involved in viral membrane fusion and ion channel function provide new insights into therapeutic design and proteins as potential targets of antivirals. Here we give three typical viral membrane fusion proteins as examples to review the mechanisms of viral membrane fusion and viral ion channel function and the strategies of an