鉴定在细胞培养中对埃博拉病毒具有协同作用的已批准药物组合。
Identification of Combinations of Approved Drugs With Synergistic Activity Against Ebola Virus in Cell Cultures.
机构信息
Integrated Research Facility, Division of Clinical Research, Frederick.
Department of Cell Biology, University of Virginia, Charlottesville.
出版信息
J Infect Dis. 2018 Nov 22;218(suppl_5):S672-S678. doi: 10.1093/infdis/jiy304.
BACKGROUND
A need to develop therapeutics to treat Ebola virus disease patients in remote and resource-challenged settings remains in the wake of the 2013-2016 epidemic in West Africa. Toward this goal, we screened drugs under consideration as treatment options and other drugs of interest, most being small molecules approved by the Food and Drug Administration. Drugs demonstrating in vitro antiviral activity were advanced for evaluation in combinations because of advantages often provided by drug cocktails.
METHODS
Drugs were screened for blockade of Ebola virus infection in cultured cells. Twelve drugs were tested in all (78 pair-wise) combinations, and 3 were tested in a subset of combinations.
RESULTS
Multiple synergistic drug pairs emerged, with the majority comprising 2 entry inhibitors. For the pairs of entry inhibitors studied, synergy was demonstrated at the level of virus entry into host cells. Highly synergistic pairs included aripiprazole/piperacetazine, sertraline/toremifene, sertraline/bepridil, and amodiaquine/clomiphene.
CONCLUSIONS
Our study shows the feasibility of identifying pairs of approved drugs that synergistically block Ebola virus infection in cell cultures. We discuss our findings in terms of the theoretic ability of these or alternate combinations to reach therapeutic levels. Future research will assess selected combinations in small-animal models of Ebola virus disease.
背景
在 2013-2016 年西非埃博拉疫情之后，仍需要开发治疗药物，以治疗偏远和资源有限环境中的埃博拉病毒病患者。为此，我们筛选了正在考虑的治疗选择药物和其他有兴趣的药物，其中大多数是食品和药物管理局批准的小分子药物。由于药物鸡尾酒通常提供的优势，具有体外抗病毒活性的药物被推进进行组合评估。
方法
在培养的细胞中筛选药物以阻断埃博拉病毒感染。总共测试了 12 种药物（78 对）的所有组合，有 3 种药物在部分组合中进行了测试。
结果
出现了多种协同药物对，其中大多数包含 2 种进入抑制剂。对于研究的进入抑制剂对，协同作用在病毒进入宿主细胞的水平上得到了证明。高度协同的对包括阿立哌唑/哌醋甲酯、舍曲林/托瑞米芬、舍曲林/贝普地尔和阿莫地喹/氯米芬。
结论
我们的研究表明，在细胞培养物中识别协同阻断埃博拉病毒感染的已批准药物对是可行的。我们根据这些或其他组合在达到治疗水平方面的理论能力讨论了我们的发现。未来的研究将在埃博拉病毒病的小动物模型中评估选定的组合。
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