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Synergistic drug combination effectively blocks Ebola virus infection.
- Source :
-
Antiviral research [Antiviral Res] 2017 Jan; Vol. 137, pp. 165-172. Date of Electronic Publication: 2016 Nov 24. - Publication Year :
- 2017
-
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.<br /> (Published by Elsevier B.V.)
- Subjects :
- Animals
Cell Line
Chlorocebus aethiops
Clarithromycin pharmacology
Drug Combinations
Drug Synergism
Hemorrhagic Fever, Ebola drug therapy
Hemorrhagic Fever, Ebola virology
High-Throughput Screening Assays
Humans
Mefloquine pharmacology
Sphingomyelin Phosphodiesterase antagonists & inhibitors
Sphingomyelin Phosphodiesterase drug effects
Toremifene pharmacology
Triazoles pharmacology
Vero Cells
Antiviral Agents pharmacology
Ebolavirus drug effects
Virus Internalization drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9096
- Volume :
- 137
- Database :
- MEDLINE
- Journal :
- Antiviral research
- Publication Type :
- Academic Journal
- Accession number :
- 27890675
- Full Text :
- https://doi.org/10.1016/j.antiviral.2016.11.017