An equine iPSC-based phenotypic screening platform identifies pro- and anti-viral molecules against West Nile virus

Marielle Cochet, François Piumi, Kamila Gorna, Noémie Berry, Gaëlle Gonzalez, Anne Danckaert, Nathalie Aulner, Odile Blanchet, Stéphan Zientara, Francesc Xavier Donadeu, Hélène Munier-Lehmann, Jennifer Richardson, Alexandra Benchoua, Muriel Coulpier

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Outbreaks of West Nile virus (WNV) occur periodically, affecting both human and equine populations. There are no vaccines for humans, and those commercialised for horses do not have sufficient coverage. Specific antiviral treatments do not exist. Many drug discovery studies have been conducted, but since rodent or primate cell lines are normally used, results cannot always be transposed to horses. There is thus a need to develop relevant equine cellular models. Here, we used induced pluripotent stem cells to develop a new in vitro model of WNV-infected equine brain cells suitable for microplate assay, and assessed the cytotoxicity and antiviral activity of forty-one chemical compounds. We found that one nucleoside analog, 2'C-methylcytidine, blocked WNV infection in equine brain cells, whereas other compounds were either toxic or ineffective, despite some displaying anti-viral activity in human cell lines. We also revealed an unexpected proviral effect of statins in WNV-infected equine brain cells. Our results thus identify a potential lead for future drug development and underscore the importance of using a tissue- and species-relevant cellular model for assessing the activity of antiviral compounds.

Original languageEnglish
Article number32
Pages (from-to)1-13
Number of pages13
JournalVeterinary Research
Issue number32
Early online date16 Mar 2024
Publication statusPublished - 16 Mar 2024

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Horses
  • Humans
  • West Nile virus
  • Induced Pluripotent Stem Cells
  • West Nile Fever/veterinary
  • Brain
  • Antiviral Agents/pharmacology
  • Horse Diseases/drug therapy


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