Although a group of FDA-approved drugs were previously identified with activity against Ebola virus (EBOV), most of them are not clinically useful because their human blood concentrations are not high enough to inhibit EBOV infection. We screened 795 unique three-drug combinations in an EBOV entry assay. Two sets of three-drug combinations, toremifene-mefloquine-posaconazole and toremifene-clarithromycin-posaconazole, were identified that effectively blocked EBOV entry and were further validated for inhibition of live EBOV infection. The individual drug concentrations in the combinations were reduced to clinically relevant levels. We identified mechanisms of action of these drugs: functional inhibitions of Niemann-Pick C1, acid sphingomyelinase, and lysosomal calcium release. Our findings identify the drug combinations with potential to treat EBOV infection.

中文翻译：

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协同药物联合有效阻断埃博拉病毒感染。

尽管先前已确定一组FDA批准的药物具有抗埃博拉病毒（EBOV）的活性，但由于它们的人血浓度不足以抑制EBOV感染，因此大多数药物在临床上均无用。我们在EBOV进入试验中筛选了795种独特的三药组合。确定了两组三药组合：托瑞米芬-甲氟喹-泊松康唑和托瑞米芬-克拉霉素-泊康康唑，这些药有效地阻止了EBOV的进入，并进一步验证了其对活EBOV感染的抑制作用。组合中的单个药物浓度降低至临床相关水平。我们确定了这些药物的作用机理：Niemann-Pick C1，功能性神经鞘磷脂酶和溶酶体钙释放的功能抑制。