Inhibitors of the sodium potassium ATPase that impair herpes simplex virus replication identified via a chemical screening approach
Inhibitors of the sodium potassium ATPase that impair herpes simplex virus replication identified via a chemical screening approach
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DOI：
10.1016/j.virol.2007.05.001
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发表时间：
2007-09-30
期刊：
影响因子：
3.7
通讯作者：
Coen, Donald M.
中科院分区：
文献类型：
--
作者：
Dodson, Allen W.;Taylor, Travis J.;Coen, Donald M.
小分子可以为研究病毒生物学提供有价值的工具。我们开发了一种化学筛选方法，利用与早期蛋白融合的绿色荧光蛋白来鉴定单纯疱疹病毒感染中尚不清楚的早期前基因表达步骤的小分子抑制剂。我们的分析确定了哇巴因，一种强心苷。在过夜试验中，哇巴因可逆地降低病毒产量100倍，而不影响细胞代谢活性。其他强心苷的抗病毒效力与其对这些化合物的已知靶点细胞钠钾ATP酶的效力相关。如果在感染后8 h加入，哇巴因的作用降低。它不抑制病毒附着或进入，但确实使病毒立即早期和早期基因的表达降低至少5倍。总的来说，这些结果暗示了迄今为止被认为对病毒基因表达之前的HSV复制阶段不重要的细胞靶标。(C)2007爱思唯尔公司All rights reserved.
Small molecules can provide valuable tools to investigate virus biology. We developed a chemical screening approach to identify small molecule inhibitors of poorly understood, pre-early gene expression steps in her-pes simplex virus infection, using green fluorescent protein fused to an early protein. Our assay identified ouabain, a cardiac glycoside. Ouabain reversibly decreased viral yield by 100-fold without affecting cellular metabolic activity in an overnight assay. The antiviral potencies of other cardiac glycosides correlated with their potencies against the known target of these compounds, the cellular sodium potassium ATPase. Ouabain had a reduced effect if added 8 h post-infection. It did not inhibit viral attachment or entry, but did reduce the expression of viral immediate-early and early genes by at least 5-fold. Collectively, these results implicate a cellular target that was hitherto not considered important for a stage of HSV replication prior to viral gene expression. (C) 2007 Elsevier Inc. All rights reserved.