• Wei Sun, Shihua He, Carles Martínez-Romero, Jennifer Kouznetsova, Gregory Tawa, Miao Xu, Paul Shinn, Ethan Fisher, Yan Long, Omid Motabar, Shu Yang, Philip E Sanderson, Peter R Williamson, Adolfo García-Sastre, Xiangguo Qiu, and Wei Zheng.
• National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda MD 20892, USA.
• Antiviral Res. 2017 Jan 1; 137: 165-172.

AbstractAlthough 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.Published by Elsevier B.V.

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