Synergistic drug combination effectively blocks Ebola virus infection

Antiviral Res. 2017 Jan;137:165-172. doi: 10.1016/j.antiviral.2016.11.017. Epub 2016 Nov 24.


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.

Keywords: Drug combination; Drug repurposing; Ebola prevention; Ebola treatment; Polypharmacology.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Chlorocebus aethiops
  • Clarithromycin / pharmacology
  • Drug Combinations
  • Drug Synergism
  • Ebolavirus / drug effects*
  • 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
  • Virus Internalization / drug effects*


  • Antiviral Agents
  • Drug Combinations
  • Triazoles
  • posaconazole
  • Toremifene
  • acid sphingomyelinase-1
  • Sphingomyelin Phosphodiesterase
  • Clarithromycin
  • Mefloquine