流感病毒血凝素活性肽抗流感病毒感染的机制研究及结构优化

项目名称： 流感病毒血凝素活性肽抗流感病毒感染的机制研究及结构优化

项目编号： No.81202568

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 陈勍

作者单位： 中国医学科学院药物研究所

项目金额： 24万元

中文摘要： 流感的频发使各国都将新型抗流感药物作为研究重点。流感病毒表面的血凝素蛋白（HA）与宿主细胞表面唾液酸（SA）受体相互作用介导病毒进入细胞是流感病毒感染的第一步，阻断其作用就可有效抑制病毒感染。目前国内外均没有以病毒进入环节为靶点的抗流感药物问世。本项目依据流感病毒自体蛋白HA的一级序列信息，人工合成HA片段肽库，筛选寻找可与HA竞争结合受体的肽分子。我们前期研究已完成肽库的构建和筛选，成功找到8个活性肽可特异性抑制流感病毒的侵入，本项目将深入研究活性肽抑制流感病毒进入的机理，并对活性肽作结构变换，优化其药效/稳定性。多肽药物在抗流感药物领域未见报道，但在抗艾滋病药物中已实现。本项目将探索基于流感病毒HA设计的肽抑制剂作为抗流感药物的可能性，为研究新型抗流感多肽药物奠定基础。

中文关键词： 流感病毒；血凝素；活性肽；进入环节；宿主

英文摘要： The frequent outbreaks of flu around the world make the research of new anti-flu drugs a key project in global pharmaceutical field. The entry of influenza virus into host cells is the first step for infection, it starts with the binding between hemagglutinin (HA), the envelop protein of influenza virus, and the host receptor, sialic acid (SA). The interactions between HA and SA induce the invasion of virus into host cells, blocking its role can effectively inhibit viral infection.There were no drugs targeted on the entry process of influenza virus in global market so far. Based on the information of primary protein sequence of HA, the HA fragment peptide library had been constituted by our project aiming at finding the effective peptides that could compete with HA in binding the SA receptor. Our anterior research had completed the screening of HA peptide library, and we successfully found eight active peptides which could specially inhibit the entry of the influenza virus. This project will investigate the mechanism of the active peptides, and optimize the peptide structure to improve the activity and stability. Peptide drugs haven't emerged in the field of anti-flu drugs, while it had been listed in anti-HIV drugs.This research will explore the possibility of anti-flu peptide inhibitors based on the influenza

英文关键词： influenza virus；hemagglutinin；active peptide；entry；host