ABSTRACT
Background: Parasitic nematodes are a public health problem globally, and an economic burden on animal and plant agricultural industries. With their ability to generate drug resistance, new anthelmintic compounds must be constantly sourced. Methods: Using the free-living nematode, Caenorhabditis elegans, in an infrared-based motility assay, we screened 400 compounds from two open-source, small-molecule collections distributed by the Medicines for Malaria Venture, namely, the COVID Box and Global Health Priority Box. The screening assay was first validated for worm number, DMSO concentration and final volume. Results: Primary and secondary (time- and concentration-dependent) screens of both boxes, identified twelve compounds as hits; nine of which were known anthelmintics. Three novel anthelmintic hits, flufenerim, flucofuron and indomethacin were identified with EC50 values ranging from 0.211 to 23.174 M. Counter toxicity screens with HEK293 cells indicated varying degrees of toxicity with EC50 values ranging from 0.453 to >100 M. Conclusions: A C. elegans motility assay was optimized and used to screen two recently-released, small molecule libraries. One or more of these three novel active compounds might serve as starting points for the development of new anthelmintics.