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Last Updated: 18/06/2024
A fragment-based screening approach to identify, develop, and characterise novel highly potent and efficacious inhibitors against the malaria parasite uridine diphosphate galactose transporter (UGT)
Objectives
To identify and develop novel inhibitors against Plasmodium falciparum uridine-diphosphate galactose transporter (PfUGT) with robust antiplasmodial activity by determining the high-resolution atomic structure of PfUGT.
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.
Aug 2021 — Aug 2026
$1.11M
