冠状病毒主蛋白酶及其化学抑制剂研究进展  

Progress About Coronavirus Main Proteinase and Its Inhibitors

作　　者：熊清[1] 王远强[2] 李志良[1] 

机构地区：[1]重庆大学生物工程学院,重庆400030 [2]重庆大学化学化工学院,重庆400030

出　　处：《重庆大学学报（自然科学版）》2004年第6期60-64,73,共6页Journal of Chongqing University

基　　金：重庆市应用基础项目(01-3-6);国家春晖计划教育部启动基金(99-1-4/38);霍英东基金及国家新药基金资助课题(1998);重庆大学研究生创新基金资助(2003)

摘　　要：一个新的冠状病毒已经被鉴定为急性呼吸道综合症(SARS)的病原体,控制该病毒复制复合体活性的主蛋白酶(Mpro或3CLpro)将很可能成为开发针对SARS特效治疗药物的靶位点。综述了人冠状病毒株229E(HCoV229E)和一种在猪体内引发传染性胃肠炎的病毒(TGEV)的Mpro的晶体结构以及以此为基础构建的SARS冠状病毒(SARS-CoV)同源蛋白酶的空间结构模型。通过对这些同源蛋白酶的结构及其与已知的蛋白酶化学抑制剂的结合特征进行分析后发现Mpro的底物结合位点具有惊人的保守性,这种保守性也被重组SARS-CoVMpro能介导的TGEVMpro的底物剪切实验所进一步证实。分子模型表明已有的鼻病毒3Cpro抑制剂经过改进后或许能用于SARS的治疗。A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (M^(pro), also called 3CL^(pro)), controlling the activities of the coronavirus replication complex, represents an attractive target for therapy. A homology model for SARS coronavirus (SARS-CoV) M^(pro), which is based on crystal structures for human coronavirus (strain 229E) M^(pro) and for an inhibitor complex of porcine coronavirus (transmissible gastroenteritis virus, TGEV) M^(pro) are reviewed. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV M^(pro)-mediated cleavage of a TGEV M^(pro) substrate. Molecular modeling suggests that available rhinovirus 3C^(pro) inhibitors may be modified to make them useful for SARS therapy.

关 键 词：冠状病毒 急性呼吸道综合症 主蛋白酶 晶体结构 抑制剂 

分 类 号：Q5[生物学—生物化学]