原标题：【文献】Viruses：一类化合物VPI 可以有效的抑制水泡性口炎病毒(VSV)

近日，Tomoaki Ogino 研究团队在viruses杂志发表研究论文《Vesiculopolins, a New Class of Anti-Vesiculoviral Compounds, Inhibit Tranion Initiation of Vesiculoviruses 》发现了一类化合物VPI 可以有效的抑制水泡性口炎病毒(VSV),且对细胞的活性无明显影响。

基于50000个小分子组成的chembridge文库，通过细胞的高通量筛选测定法，获得一种可以有效抑制VSV病毒复制的一类化合物，命名为vesululopolins，简称VPI，该化合物的芳香基团4号位的结构可以是多样的（结构如图D），但是综合分析结果显示A,B类的结构的效果最优。

为了进一步的揭示VPI的抗病毒活性的原理，研究者选用了抗病毒活性最高、毒性最小的VPI A用于后续的实验，发现VPI A靶向多功能RNA依赖性RNA聚合酶（RdRp）L蛋白的聚合酶结构域，从而抑制了LeRNA和mRNA的合成，对病毒进行高效杀伤。

这些结果表明，VPI不仅可以用作阐明水泡病毒转录机制的分子探针，而且还可以作为开发抗水泡病毒和其他相关弹状病毒的抗病毒药物的先导化合物。

Abstract

Vesicular stomatitis virus (VSV) represents a promising platform for developing oncolytic viruses, as well as vaccines against significant human pathogens. To safely control VSV infection in humans, small-molecule drugs that selectively inhibit VSV infection may be needed.

Here, using a cell-based high-throughput screening assay followed by an in vitro tranion assay, compounds with a 7-hydroxy-6-methyl-3,4-dihydroquinolin-2(1H)-one structure and an aromatic group at position 4 (named vesiculopolins, VPIs) were identified as VSV RNA polymerase inhibitors.

The most effective compound, VPI A, inhibited VSV-induced cytopathic effects and in vitro mRNA synthesis with micromolar to submicromolar 50% inhibitory concentrations.

VPI A was found to inhibit terminal de novo initiation rather than elongation for leader RNA synthesis, but not mRNA capping, with the VSV L protein, suggesting that VPI A is targeted to the polymerase domain in the L protein.

VPI A inhibited tranion of Chandipura virus, but not of human parainfluenza virus 3, suggesting that it specifically acts on vesiculoviral L proteins.

These results suggest that VPIs may serve not only as molecular probes to elucidate the mechanisms of tranion of vesiculoviruses, but also as lead compounds to develop antiviral drugs against vesiculoviruses and other related rhabdoviruses.

本期编辑：苏复

素材来源：复百澳生物

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