调控流感病毒与宿主细胞识别的传统中药活性成分及其分子机制研究

项目名称： 调控流感病毒与宿主细胞识别的传统中药活性成分及其分子机制研究

项目编号： No.81202975

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 于茂荣

作者单位： 北京大学

项目金额： 23万元

中文摘要： 以病毒进入细胞为靶点的抗病毒药物研究，是克服和延缓RNA病毒自身基因高突变带来耐药性的有效途径。前期工作表明白前、白薇、板蓝根和川续断的醇提物的正丁醇部位可显著抑制流感病毒和丙肝病毒进入细胞，进一步分离出的某些五环三萜类苷元也表现出一定的抑制活性，显示出皂苷类物质在抑制病毒进入细胞方面的应用前景。我们将继续借助高致病性流感病毒假病毒感染模型，追踪和分离传统中药中抗高致病性流感病毒的活性成分（群），并利用生物素标记活性成分、病毒血凝素（HA）与细胞结合试验、以及HA与细胞融合试验等现代生物学方法揭示皂苷类药物的抗病毒作用靶蛋白和分子机制，尤其在天然物质调控蛋白-蛋白相互作用从而调控病毒与宿主的识别机理方面。同时，利用已建立的假病毒筛选系统，研究活性成分对其它种属病毒的广谱抗病毒作用。本研究对于研制高效、低毒、广谱的抗病毒药物，阐明传统中药抗病毒作用机理及新药物靶点的发现都具有重要的意义。

中文关键词： 流感病毒；三萜皂苷；作用机制；；

英文摘要： Drug development targeting virus entry is an efficient approach to overcoming drug resistence caused by mutations of RNA viruses. The previous study found that saponins from Cynanchum glaucescens, Cynanchum atratum, Radix isatidis and Dipsacus asper Wall significantly inhibited the viral entry, including influenza virus, HCV, and so on. The pentacyclic triterpene obtained by subsequent isolation also exhibited strong anti-viral activity, indicating that the saponins from traditional Chinese medicine (TCM) are potential drugs capable of preventing viral entry into target cells. In this project, we will isolate and identify active compounds from TCM which strongly inhibit highly pathogenic influenza virus based on the pseudovirus system, adopt the biotin-label technology to find the target protein, use HA assay to analyze the inhibiting effect of active compounds on virus-host cell interaction, and utilize the polykaryon assay to examine the virus-cell fusion inhibitory activity of the drugs. We will perform various molecular biology experiments to discover the mechanism of anti-virus activity of such drugs, especially the mechanism to the regulation of drugs on the recognition between virus and host cells via interaction between viral and cellular proteins. Then, we will examine whether the drugs are broad-spect

英文关键词： Influenza virus；triterpene saponins；mechanism；；