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应用多种组学和网络投影分析进行病原体蚊媒病毒的药物重定位。

Application of multiple omics and network projection analyses to drug repositioning for pathogenic mosquito-borne viruses.

机构信息

Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, 135-0064, Japan.

Molecular Profiling Research Center for Drug Discovery (Molprof), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, 135-0064, Japan.

出版信息

Sci Rep. 2021 May 12;11(1):10136. doi: 10.1038/s41598-021-89171-x.

Abstract

Pathogenic mosquito-borne viruses are a serious public health issue in tropical and subtropical regions and are increasingly becoming a problem in other climate zones. Drug repositioning is a rapid, pharmaco-economic approach that can be used to identify compounds that target these neglected tropical diseases. We have applied a computational drug repositioning method to five mosquito-borne viral infections: dengue virus (DENV), zika virus (ZIKV), West Nile virus (WNV), Japanese encephalitis virus (JEV) and Chikungunya virus (CHIV). We identified signature molecules and pathways for each virus infection based on omics analyses, and determined 77 drug candidates and 146 proteins for those diseases by using a filtering method. Based on the omics analyses, we analyzed the relationship among drugs, target proteins and the five viruses by projecting the signature molecules onto a human protein-protein interaction network. We have classified the drug candidates according to the degree of target proteins in the protein-protein interaction network for the five infectious diseases.

摘要

虫媒病毒病原体是热带和亚热带地区严重的公共卫生问题,在其他气候带也越来越成为一个问题。药物重定位是一种快速、药物经济学的方法,可用于识别针对这些被忽视的热带病的化合物。我们应用一种计算药物重定位方法来研究五种虫媒病毒感染:登革热病毒(DENV)、寨卡病毒(ZIKV)、西尼罗河病毒(WNV)、日本脑炎病毒(JEV)和基孔肯雅热病毒(CHIV)。我们根据组学分析为每种病毒感染确定了特征分子和途径,并通过过滤方法确定了针对这些疾病的 77 种候选药物和 146 种蛋白质。基于组学分析,我们通过将特征分子投射到人类蛋白质-蛋白质相互作用网络上,分析了药物、靶蛋白和五种病毒之间的关系。我们根据候选药物在五种传染病的蛋白质-蛋白质相互作用网络中靶蛋白的程度对其进行了分类。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e45/8115341/a77b4559d185/41598_2021_89171_Fig1_HTML.jpg

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