冠状病毒主蛋白酶结构的系统研究及在分类学上的应用

项目名称： 冠状病毒主蛋白酶结构的系统研究及在分类学上的应用

项目编号： No.31300150

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 杨海涛

作者单位： 天津大学

项目金额： 23万元

中文摘要： 冠状病毒亚科包含约三十种病毒，它们可感染人、畜，严重危害人类健康并造成畜牧业的重大损失。作为一类高传染性的病毒，它们可引发急性呼吸系统综合征（SARS）、普通感冒、肺炎、细支气管炎等人类疾病。随着新发（出）现的冠状病毒的种类的不断增多，病毒学家在如何对它们进行分类的问题上曾出现过不同的意见。通过分析发现，尽管不同的冠状病毒之间具有大大小小的差异，但它们都编码一种主蛋白酶。该酶在病毒基因复制和转录过程中起关键调控作用，亦是一个重要的药物设计靶点。由于该酶在药物设计中的重要意义，多种冠状病毒的主蛋白酶的结构也被陆续解析。本项目希望继续解析一系列与人、畜相关的主蛋白结构，对今后的药物开发提供结构基础；同时，我们将以冠状病毒主蛋白酶的三维空间结构的差异为依据，另辟蹊径用以分类学研究，从另一个角度在进化上对各种冠状病毒进行分类。

中文关键词： 冠状病毒；主蛋白酶；分类学；结构；非典

英文摘要： The subfamily Coronavirinae contains around 30 speices, which infect both human and animals, causing prevalent diseases and often severe or fatal in hosts. As highly infecious pathogens, coronaviruses cause upper and lower respiratory tract infections in humans, including common colds, bronchiolitis, and pneumonia and also various severe diseases in stock leading to great ecnomic loss. With emerging new speices of coroanviruses, virologists have ever held different opinios towards classification of various pieces of coronaviruses. Nonetheless a prevalent main protease has been identified within the genomes of various spieces of coroanviruses. This protease plays a pivital role in viral transcription and replication, making it an important drug target. For the sake of its significance, a series of structures of coroanviral main proteases has been solved for rational drug design against coronaviruses.We propose to determine a batch of unknown main protease structures of coronaviruses relevant to human and animal diseases, providing structural basis for wide-spectrum inhibitor development. Besides, based on the structural difference among a variety of coroanviruses, we would like to provide an alternative method to categorize the members within this subfamily during evolution.

英文关键词： coronavirus；main proease；taxonomy；structure；SARS