基于天然黄酮骨架的流感神经氨酸酶抑制剂的设计

项目名称： 基于天然黄酮骨架的流感神经氨酸酶抑制剂的设计

项目编号： No.21202110

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 有机化学

项目作者： 孙家英

作者单位： 四川文理学院

项目金额： 25万元

中文摘要： 流感病毒是一种严重危害人类健康的急性上呼吸道传染病，已给世界经济和人类健康构成重大威胁，加之流感病毒可变异或者与其它病毒结合产生新的、高致病的、具流行能力，给流感及时诊断和预防带来了极大的困难。因此，新型抗流感病毒药物的研发已迫在眉睫。本项目为了与地方经济结合和节约新药研发的成本，充分利用天然药用植物中广泛存在的活性成分黄酮类衍生物。因此，基于天然黄酮及二氢黄酮骨架，综合利用分子对接、序列对比和同源性分析等生物信息学方法以及分子动力学研究流感病毒变异特征及此类化合物抑制流感病毒的抑制机理；同时，构建此类化合物的药效团和定量构效关系模型，应用于新化合物的设计和活性定量预测研究。综合利用高通量筛选、模型预测等优化工具，筛选得到高抑制活性的新化合物，并进行临床前研究。

中文关键词： 流感；黄酮；神经氨酸酶抑制剂；活性；定量构效关系

英文摘要： Influenza virus is a serious hazard to human health of acute upper respiratory tract infections. It has given a major threat to the world economy and human health. Because of influenza virus variation, new generated virus and highly epidemic, it is difficult to diagnose and prevent in time. Moreover, there is a rising trend toward resistance of neuraminidase inhibitors due to emergence of new influenza virus. So, it is necessary to research and develop new influenza neuraminidase inhibitors. In order to integrate into local economy and economize cost of drug research,this project will be performed. Furthermore, flavonoids derivatives exist extensively in natural medicinal plant. So, this project is developed to make full use of active components in natural medicinal plant. Inhibition mechanism of influenza virus for flavone and flavonone derivatives are investigated using molecular docking, sequence homology comparison and analysis method of bioinformatics and molecular dynamics study of influenza virus variation characteristics. At the same time, pharmacophores and quantitative structure-activity relationship models of flavone and flavonone derivatives are developed to design and predict quantitatively the activity of new compounds. New compounds with high inhibitory activity are obtained using high throughput

英文关键词： influenza；flavonoids；neuraminidase inhibitors；activity；quantitative structure-activity relationship