Department of Microbiology and Immunology , Tulane University , New Orleans , Louisiana 70112 , United States.
Zalgen Laboratories, LLC , Germantown , Maryland 20876 , United States.
J Proteome Res. 2019 Jan 4;18(1):7-17. doi: 10.1021/acs.jproteome.8b00204. Epub 2018 Nov 5.
Liquid chromatography mass spectrometry (LCMS) proteomic analyses have revealed that host proteins are often captured in extracellular virions. These proteins may play a role in viral replication or infectivity and can represent targets for broad-spectrum antiviral agent development. We utilized LCMS to determine the host protein composition of Lassa virus-like particles (LASV VLPs). Multiple host proteins incorporated in LASV VLPs are also incorporated in unrelated viruses, notably ribosomal proteins. We assembled a data set of host proteins incorporated into extracellular viral particles. The frequent incorporation of specific host proteins into viruses of diverse families suggests that interactions of these proteins with viral factors may be important for effective viral replication. Drugs that target virion-associated host proteins could affect the protein in the extracellular virion or the host cell. Compounds that target proteins incorporated into virions with high frequency, but with no known antiviral activity, were assayed in a scalable viral screening platform, and hits were tested in competent viral systems. One of these molecules, GAPDH modulating small molecule CGP 3466B maleate (Omigapil), exhibited a dose-dependent inhibition of HIV, dengue virus, and Zika virus.
液相色谱-质谱（LCMS）蛋白质组学分析表明，宿主蛋白经常被捕获在细胞外病毒粒子中。这些蛋白质可能在病毒复制或感染性中发挥作用，并可作为广谱抗病毒药物开发的靶点。我们利用 LCMS 来确定拉萨病毒样颗粒（LASV VLPs）的宿主蛋白组成。多个被纳入 LASV VLPs 的宿主蛋白也被纳入了无关的病毒中，特别是核糖体蛋白。我们组装了一个包含细胞外病毒颗粒中的宿主蛋白的数据组。特定宿主蛋白频繁地被纳入不同家族的病毒中，这表明这些蛋白质与病毒因子的相互作用可能对有效病毒复制很重要。针对病毒粒子相关宿主蛋白的药物可能会影响细胞外病毒粒子或宿主细胞中的蛋白。针对高频率但无已知抗病毒活性的病毒粒子整合蛋白的化合物在可扩展的病毒筛选平台中进行了检测，并在有能力的病毒系统中对阳性进行了测试。这些分子中的一种，即 GAPDH 调节小分子 CGP 3466B 马来酸（Omigapil），表现出对 HIV、登革热病毒和寨卡病毒的剂量依赖性抑制作用。
