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

Marielle Cochet (1) , François Piumi (1) , Kamila Gorna (1) , Noémie Berry (1) , Gaëlle Gonzalez (1) , Anne Danckaert (2) , Nathalie Aulner (2) , Odile Blanchet (3) , Stéphan Zientara (1) , Francesc Xavier Donadeu (4) , Hélène Munier-Lehmann (5) , Jennifer Richardson (1) , Alexandra Benchoua (6) , Muriel Coulpier (1)

1 VIRO - Virologie UMR1161
2 UTechS PBI - BioImagerie Photonique – Photonic BioImaging
3 CURB - Centre Universitaire de Ressources Biologiques
4 Edin. - University of Edinburgh
5 PF-CCB - Criblage chémogénomique et biologique (Plateforme) - Chemogenomic and Biological Screening Platform
6 I-STEM - Institut des cellules souches pour le traitement et l'étude des maladies monogéniques

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.

Mots clés: Equine brain neural progenitors Flavivirus antiviral statin nucleoside analog Handling; Equine; brain; neural progenitors; Flavivirus; antiviral; statin; nucleoside analog Handling

Domaines: Sciences du Vivant [q-bio]

Marielle Cochet, François Piumi, Kamila Gorna, Noémie Berry, Gaëlle Gonzalez, et al.. An equine iPSC-based phenotypic screening platform identifies pro- and anti-viral molecules against West Nile virus. Veterinary Research, 2024, 55 (1), pp.32. ⟨10.1186/s13567-024-01290-1⟩. ⟨hal-04568823⟩