Molecular modeling of plant metabolites with anti-Onchocerca activity

Onchocerciasis or river blindness is a parasitic disease of man, caused by the filarial worm Onchocerca volvulus. It afflicts an estimated 37 million people, among whom 300,000 are blind and an additional 500,000 are visually impaired. The only class of drug targets whose X-ray crystal structure has been solved is the glutathione transferases, co-crystallized with a cofactor and a competitive inhibitor (glutathione and S-hexylglutathione). In a quest to identify potential hit compounds for drug discovery and to further explore potential inhibitory mechanisms of plant-derived anti-Onchocerca compounds, we have carried out an in silico study. The goal has been to devise molecular modeling approaches for virtual screening simulations, which could lead to the identification of potential inhibitors of this drug target from plant chemical libraries. Docking studies have been carried out for eight known plant-derived compounds showing in vitro activities against Onchocerca species. The computed binding affinities of the naturally occurring anti-Onchocerca compounds are comparable to the known co-crystallized inhibitor. Our study has laid a foundation for further investigations of naturally occurring O. volvulus drug targets. Explorations of the protein–ligand interactions from the docking poses have provided insight for potential binding interactions of interest, which could be exploited in searching for lead compounds.