Synergistic drug combination effectively blocks Ebola virus infection
Autor: | Paul Shinn, Wei Sun, Miao Xu, Xiangguo Qiu, Gregory J. Tawa, Carles Martínez-Romero, Shu Yang, Ethan G. Fisher, Philip E. Sanderson, Omid Motabar, Yan Long, Wei Zheng, Shihua He, Jennifer Kouznetsova, Peter R. Williamson, Adolfo García-Sastre |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Drug media_common.quotation_subject 030106 microbiology Pharmacology medicine.disease_cause Antiviral Agents Article Cell Line 03 medical and health sciences Clarithromycin Virology Chlorocebus aethiops medicine Animals Humans Vero Cells media_common Ebolavirus Ebola virus Mefloquine business.industry Drug Synergism Hemorrhagic Fever Ebola Triazoles Virus Internalization High-Throughput Screening Assays Drug Combinations Drug repositioning Sphingomyelin Phosphodiesterase 030104 developmental biology Vero cell Toremifene Acid sphingomyelinase NPC1 business medicine.drug |
Zdroj: | Antiviral Research. 137:165-172 |
ISSN: | 0166-3542 |
Popis: | 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. |
Databáze: | OpenAIRE |
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