Authors

R H Clare¹; J Bibby²; N Berry²; P O'Neill²; L Myhill¹; A Cassidy¹; K L Johnston¹; L Ford¹; M J Taylor¹; S A Ward¹;  ¹ Liverpool School of Tropical Medicine;  ² University of Liverpool

Discussion

The A·WOL consortium has completed the screening of a ~500,000 compound library from the Medicines for Malaria Venture, against the Wolbachia endosymbiont bacterial target of the filarial nematodes which cause of lymphatic filariasis (elephantiasis) and onchocerciasis (river blindness). This screening was completed using two methods. Cheminformatics and virtual screening (VS) methods were initially used to prioritise the screening resulting in 56,000 compounds screened over 18 months. Once an industrial scale high throughput assay became available the remaining ~495,000 compounds were screened within just 2 months. The screen delivered 1,256 anti-Wolbachia hits which have been prioritised into 11 major chemical clusters (2 to 41 compounds/cluster). Representative compounds have been selected (2-6 compounds/cluster) and are currently undergoing dose response testing. Targeting this endosymbiotic bacteria provides a macrofilaricidal (death of the adult worm) treatment for lymphatic filariasis and onchocerciasis, which together infect 150 million people worldwide.