Parasite proteins targeted by the medicines for malaria ventures (MMV) malaria box: identification, functional and structural validation

• Main Author: Chung, Zara Shi Ying
• Other Authors: Julien Lescar
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2024
• Subjects: Medicine, Health and Life Sciences
• Online Access: https://hdl.handle.net/10356/181844
• Institution: Nanyang Technological University

Malaria is a mosquito-borne disease with huge global disease mortality and morbidity. Research and development of new anti-malarial drug development are essential in light of resistance to current first-line therapies. Here, we identified Plasmodium falciparum purine nucleoside phosphorylase as the target of MMV000848. Through biochemical and structural validation, the Malaria Box compound MMV000848 is shown to bind and inhibit PfPNP activity without inhibiting the human orthologue. These findings allow for structural modifications and development of more potent PfPNP-specific analogues based on analysed enzyme-inhibitor interactions of newly presented and previously existing PNP inhibitors.