Résumé
In this study, the anti-schistosomal activity of 39 Homo sapiens Lysine Specific Demethylase 1 (HsLSD1) inhibitors was investigated on parasitic life cycle stages associated with both definitive and intermediate host infection. Amongst this collection of small molecules, compound 33 was the most potent and reduced ex vivo viabilities of schistosomula, juveniles, miracidia and adults. At its sub-lethal concentration to adults (3.13 µM), compound 33 also significantly impacted oviposition, ovarian as well as vitellarian architecture and gonadal/neoblast stem cell proliferation. ATAC-seq analysis of adults demonstrated that compound 33 significantly affected chromatin structure (intragenic regions > intergenic regions), especially in genes differentially expressed in cell populations (e.g., germinal stem cells, hes2+stem cell progeny, S1 cells and late female germinal cells) linked to these ex vivo phenotypes. The data presented here allow for visualisation in IGV https://igv.org/app/ Produced in collaboration with IHPE.