Drug Discovery

We focus on discovering new antimalarial compounds that target unexplored biology in the parasite and that show low risk of developing resistance. We are particularly interested in compounds with added transmission-blocking activity, i.e. compounds able to either kill gametocytes or gametes and thereby prevent transmission to mosquitoes. Whilst malaria therapeutics must be able to kill the asexual pathogenic forms of malaria parasites, very few of them effectively kill the transmissible, gametocyte forms of the parasite and are essentially not useful to block the spread of the disease. To contribute to global malaria elimination, we therefore try and find new transmission-blocking antimalarials. We use our biological knowledge to identify the gametocyte’s weak spots to effectively and specifically kill these forms of the parasite.

We explore a new candidate's mode of action by determining the compound's risk of resistance (MIR assay), performing in vitro resistance selections for resistance mechanism/target identification, chemical proteomics for target identification and using morphological and transcriptomic fingerprinting to define action. 

Projects are funded by the  Medicines for Malaria Venture, the BMGF and LifeArc though the Grand Challenges African Drug Discovery Accelerator, the South African DSI & Medical Research Council Strategic Health Innovation Partnership (SHIP) with the Medicines for Malaria Venture.

We have the largest and most specialised transmission-blocking screening platform in Africa, the Drug Discovery for Malaria Elimination Platform (DMEP).  We can analyse compounds for asexual blood stage activity, stage-specific gametocytocidal activity, male and female gamete activity and (with WITS University), an artificial mosquito feeding system and counterscreen for toxicitiy.  his platform supports all ongoing antimalarial drug discovery programs in South Africa and Africa. 

We run the Medicines for Malaria Venture Global Test Centre for  stage-specific gametocytocidal action.  We evaluate frontrunner antimalarial candidates in the MMV portfolio and with MMV project partners to provide data on the activity of such compounds on both immature and mature gametocytes.