Synergistic drug combination effectively blocks Ebola virus infection.

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2017
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Abstract
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.
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sun2017synergisticantiviral Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Sun, Wei;He, Shihua;Martínez-Romero, Carles;Kouznetsova, Jennifer;Tawa, Gregory;Xu, Miao;Shinn, Paul;Fisher, Ethan;Long, Yan;Motabar, Omid;Yang, Shu;Sanderson, Philip E;Williamson, Peter R;García-Sastre, Adolfo;Qiu, Xiangguo;Zheng, Wei;
Journal Antiviral research
Year 2017
DOI
10.1016/j.antiviral.2016.11.017
URL
Keywords
drug combination drug repurposing polypharmacology ebola prevention ebola treatment

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