A large number of Food and Drug Administration (FDA)-approved drugs have been found to inhibit the cell entry of Ebola virus (EBOV). However, since these drugs have various primary pharmacological targets, their mechanisms of action against EBOV remain largely unknown. We have previously shown that six FDA-approved drugs inhibit EBOV infection by interacting with and destabilizing the viral glycoprotein (GP). Here we show that antidepressants imipramine and clomipramine and antipsychotic drug thioridazine also directly interact with EBOV GP and determine the mode of interaction by crystallographic analysis of the complexes. The compounds bind within the same pocket as observed for other, chemically divergent complexes but with different binding modes. These details should be of value for the development of potent EBOV inhibitors.

中文翻译：

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埃博拉病毒糖蛋白复合物与三环类抗抑郁药和抗精神病药的结构

已发现大量食品和药物管理局 (FDA) 批准的药物可抑制埃博拉病毒 (EBOV) 的细胞进入。然而，由于这些药物具有不同的主要药理学靶点，它们对 EBOV 的作用机制仍然很大程度上未知。我们之前已经表明，六种 FDA 批准的药物通过与病毒糖蛋白 (GP) 相互作用并使其不稳定来抑制 EBOV 感染。在这里，我们显示抗抑郁药丙咪嗪和氯米帕明以及抗精神病药物硫利达嗪也直接与 EBOV GP 相互作用，并通过复合物的晶体学分析确定相互作用的模式。与其他化学上不同的复合物所观察到的一样，这些化合物结合在同一个口袋内，但结合模式不同。这些细节对于开发有效的 EBOV 抑制剂应该是有价值的。