基于病毒-宿主蛋白质相互作用网络的抗病毒宿主靶标辨识

项目名称： 基于病毒-宿主蛋白质相互作用网络的抗病毒宿主靶标辨识

项目编号： No.81473184

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王升启

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 80万元

中文摘要： 以病毒蛋白为靶的抗病毒药物面临易产生耐药等诸多问题，宿主分子靶向已经成目前抗病毒药物研究的重要策略，宿主靶标的辨识是宿主靶向药物设计的关键。近年来通过高通量实验技术揭示了多种病毒与其宿主之间的蛋白相互作用网络，为从系统水平上研究病毒生存策略和建立宿主靶标的理性选择方法奠定了基础。本项目拟在病毒-宿主静态网络图谱和其它高通量实验数据的基础上建立动态的病毒-宿主蛋白相互作用网络模型，将病毒感染归结为宿主网络的干扰-平衡问题，将宿主靶向抗病毒治疗归结为网络控制问题，用系统生物学的相关理论和研究方法揭示病毒-宿主相互作用的平衡条件，建立基于网络的宿主靶标辨识方法。以流感等病毒为研究对象，通过宿主分子靶向体外抗病毒活性评价实验的结果验证和修正网络模型和宿主靶标辨识算法，为抗病毒药物宿主靶标的辨识和宿主-病毒联合靶向治疗策略的设计提供新的理论基础和分析方法。

中文关键词： 蛋白质相互作用网络；病毒-宿主相互作用；宿主靶标辨识

英文摘要： Antiviral drugs targeting viral proteins have brought many problems including highly-induced resistance. Host-directed antiviral strategy has played important role in antiviral drug discovery, and the key to the design of host-directed antiviral drugs is the identification of host targets. In recent years, high-throughput screen has been developed to provide a protein-protein interaction network of multiple viruses and hosts, laying solid ground for studying viral survival strategy at system level and establishing rational screening methods of host target identification. We aim to establish a dynamic virus-host protein-protein interaction network model based on static virus-host network and other experimental data from high-throughput screening, and further, by regarding viral infection as perturbance-equilibrium problem in host network and host-directed antiviral treatment as network control problem, we try to elucidate the equilibrium conditions for virus-host interaction and establish the network-based host targets identification methods, utilizing systematic biology theory and methods. We intend to validate and modify the network model and host targets identification algorithms based on results from in vitro evaluation of the antiviral activity of host targets for influenza virus. Altogether, these shall provide new theory and analytical methods for identification of host targets for antiviral drugs and design of host-virus combined targeted therapy.

英文关键词： protein interaction network;virus-host interaction;host target identification