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.

中文翻译：

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在细胞外病毒颗粒中鉴定出的宿主蛋白可作为广谱抗病毒抑制剂的靶标。

液相色谱质谱（LCMS）蛋白质组学分析表明，宿主蛋白通常被捕获在细胞外病毒体中。这些蛋白质可能在病毒复制或感染性中起作用，并且可以代表广谱抗病毒剂开发的目标。我们利用LCMS确定Lassa病毒样颗粒（LASV VLP）的宿主蛋白组成。掺入LASV VLP中的多种宿主蛋白​​也掺入无关病毒中，尤其是核糖体蛋白。我们组装了整合到细胞外病毒颗粒中的宿主蛋白的数据集。特定宿主蛋白频繁掺入不同家族的病毒中表明，这些蛋白与病毒因子的相互作用可能对有效的病毒复制很重要。靶向与病毒体相关的宿主蛋白的药物可能会影响细胞外病毒体或宿主细胞中的蛋白。在可扩展的病毒筛选平台中测定了靶向以高频率掺入到病毒粒子中的蛋白质的化合物，但没有已知的抗病毒活性，并在有效的病毒系统中测试了命中。这些分子之一，GAPDH调节小分子CGP 3466B马来酸酯（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。