Target identification and validation for anthelmintic discovery

Abstract

Anthelmintics presently used in humans were discovered using empirical biological screening processes targeting helminths of veterinary importance. The modern approach to drug discovery is based on genetic, bioinformatic and genomic identification of protein targets followed by specific validation assays and high-throughput screening using chemical libraries. Existing broad-spectrum anthelmintics bind just three classes of molecular targets; more classes of targets are urgently needed. In the absence of robust functional genomics technologies for helminth parasites, the technology of RNA interference in parasites and in the model Caenorhabditis elegans is the best available for discovery and validation of new targets. This article outlines and critically discusses an idealised drug discovery pipeline for anthelmintic discovery in nematodes.