Omics-Driven Knowledge-Based Discovery of Anthelmintic Targets and Drugs

Abstract Helminths are among the most important parasites of humans and economically important plants and animals. Existing drugs targeting helminths (anthelmintics) typically belong to only a few classes of molecules and they target a small set of proteins and biological processes in these parasites, resulting in widespread multidrug resistance and creating a need to develop new anthelmintics. Due to challenges specific to working with parasitic helminths, molecular and genetic data relevant to most helminths were relatively sparse until recently. Fortunately, the advent of next-generation sequencing resulted in the accumulation of large amounts of omics data, which in combination with chemogenomic screening and the development of high-throughput screening techniques for certain helminth species and Caenorhabditis elegans has now made it possible to conduct multiomics, data-driven, large-scale searches for novel targets and to experimentally test drugs and drug-like compounds associated with them. Here we describe the current state of this field (with a focus on parasitic nematodes), the factors to be considered in these approaches, the challenges that still need to be overcome and possible future directions that are expected to yield multiple potential drugs effective against these heretofore neglected tropical diseases.