Searching for Drugs That Target Multiple Receptors for Anthelmintics from African Natural Products

Abstract

Assay strategies that permit mechanism-based screening for new antiparasitic drugs on-site have been established at the Universities of Botswana and Cape Town. Researchers at these sites can take advantage of the chemical and biological diversity found in Africa to identify lead compounds for use against parasitic nematodes of local importance. The platform employs recombinant strains of yeast which express parasite proteins in a context that makes the survival of the microbe dependent on the function of the parasite drug target. African natural products can be subjected to high-throughput screening campaigns for discovery of compounds that selectively act on these parasite proteins. Yeast strains functionally expressing nematode G-protein-coupled receptors (GPCRs) allow detection of novel anthelmintic leads that interact with multiple receptors, reducing the chances of selecting drug-resistant parasite populations. Screening collections of African bio-extracts, to identify non-peptide ligands that target parasite GPCRs, provides local control of intellectual property rights, creating an economically sustainable platform. Revenues derived from agreements for leads for other indications of global economic value can fund further work to explore the chemistry embodied in the biodiversity of Africa to expand this platform beyond parasitic infections.