Centre for Research in Infectious Diseases (CRID), Cameroon: A fragment-based screening approach to identify, develop, and characterise novel highly potent and efficacious inhibitors against the malaria parasite uridine diphosphate galactose transpor

Malaria is a life-threatening disease that leads to the death of over 400,000 people annually and affects an estimated 229 million people worldwide. Approximately 3 billion USD is spent annually on malaria control. Human antibodies generated against the parasites do not provide sterilising immunity. Artemisinin-based combination therapies are recommended by the WHO but the therapeutic benefits are threatened by drug-resistance. Thus, there is an urgent need to develop novel treatments. Previous studies in malaria identified the Plasmodium falciparum uridine-diphosphate galactose transporter (PfUGT) as a drug target. PfUGT is a membrane transporter that supplies uridine-diphosphate galactose (UDP-Gal) to all stages of the parasite's life cycle in humans. The transport of UDP-Gal across the endoplasmic reticulum and Golgi membranes to their respective lumina is essential for parasite survival, virulence, and pathogenicity. I aim to identify and develop novel inhibitors against PfUGT with robust antiplasmodial activity. I will begin by determining the high-resolution atomic structure of PfUGT. I will then identify and optimise inhibitors that bind to PfUGT and disrupt UDP-Gal transport, thus killing the parasite.

Programme: International Intermediate Fellowship

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