High-throughput phenotypic screening of Medicines for Malaria Venture's Hit Generation Library 1 identifies new nematocidal chemotypes

Abstract

Parasitic helminths impose substantial health and economic burdens on humans and livestock, and widespread resistance to existing anthelmintic classes underscores the urgent need for new chemotypes with distinct mechanisms of action as part of integrated parasite control strategies. Here, we performed a large-scale phenotypic screen of the Medicines for Malaria Venture Hit Generation Library 1 (HGL1), testing 139,916 compounds (98.7% of the 141,786-compound library) against exsheathed third-stage larvae of Haemonchus contortus, with selective cross-species evaluation in Caenorhabditis elegans. Using infrared-based motility and developmental assays in 384-well format, the platform delivered e..