Chemical perturbation reveals a cytoskeletal-trafficking vulnerability in Haemonchus contortus.

Abstract

The control of parasitic nematodes of humans and animals remains heavily dependent on a limited number of anthelmintic drug classes, and resistance to major classes is now widespread. Although phenotypic screening readily identifies compounds that impair worm motility or development, the intrinsic biological processes underlying chemical sensitivity in parasitic nematodes remain poorly defined. Here, we identified a hit compound with a pyridyl scaffold from a phenotypic screen against the model parasitic nematode, Haemonchus contortus, and using structure-activity optimisation we generated a potent chemical probe, WEHI-684. To uncover protein networks associated with the mechanism of action,..