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Peer-reviewedCC BY 4.0Virus Research

Identification of small molecule inhibitors of Ebola virus by use of a biologically contained virus system

  1. 1Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53706, USA

Abstract

Ebola virus disease is a severe illness with high mortality for which limited therapeutic options are available. Identifying new antiviral drugs that target viral proteins is essential for improving prevention and treatment strategies. In this study, we screened a library of 2620 small molecules enriched for reported inhibitory activity against cellular and viral helicases to identify phenotypic inhibitors of a biologically contained virus, Ebola∆VP30 virus, in Vero cells stably expressing VP30 protein. Seven compounds significantly reduced virus titers at least 100-fold with minimal cytotoxicity and demonstrated low IC50 values. Two of these compounds completely inhibited EbolaΔVP30 virus infection, interfering with either virus entry or replication. Although these preliminary screening hits require further optimization and in vivo validation, their identification opens new avenues for anti-Ebola virus drug discovery.

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BibTeX
@article{amare2026identification,
  title = {{Identification of small molecule inhibitors of Ebola virus by use of a biologically contained virus system}},
  author = {Meareg G. Amare and Peter J. Halfmann},
  journal = {Virus Research},
  year = {2026},
  month = oct,
  doi = {10.1016/j.virusres.2026.199823},
  url = {https://doi.org/10.1016/j.virusres.2026.199823},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Identification of small molecule inhibitors of Ebola virus by use of a biologically contained virus system
AU  - Meareg G. Amare
AU  - Peter J. Halfmann
PY  - 2026
DA  - 2026/10/25
JO  - Virus Research
DO  - 10.1016/j.virusres.2026.199823
UR  - https://doi.org/10.1016/j.virusres.2026.199823
AB  - Ebola virus disease is a severe illness with high mortality for which limited therapeutic options are available. Identifying new antiviral drugs that target viral proteins is essential for improving prevention and treatment strategies. In this study, we screened a library of 2620 small molecules enriched for reported inhibitory activity against cellular and viral helicases to identify phenotypic inhibitors of a biologically contained virus, Ebola∆VP30 virus, in Vero cells stably expressing VP30 protein. Seven compounds significantly reduced virus titers at least 100-fold with minimal cytotoxicity and demonstrated low IC50 values. Two of these compounds completely inhibited EbolaΔVP30 virus infection, interfering with either virus entry or replication. Although these preliminary screening hits require further optimization and in vivo validation, their identification opens new avenues for anti-Ebola virus drug discovery.
SN  - 0168-1702
SN  - 1872-7492
ER  -