Project Grant R21AI201386

The National Institute of Allergy and Infectious Diseases, a component of the Department of Health and Human Services National Institutes of Health, awarded Purdue University $239,023 on August 21, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop covalent phosphatidylinositol 4-kinase (PI4K) inhibitors targeting malaria parasites.

The project executes hit-to-lead optimization of high-priority molecular scaffolds against Plasmodium species that inhibit PI4KIIIB through an irreversible mechanism of action. The research team identified a nucleophilic cysteine residue in Plasmodium PI4KIIIB exploitable for drug design and hypothesizes that irreversible inhibitors will overcome off-target kinase selectivity liabilities observed in prior reversible inhibitor clinical trials. Deliverables include evaluation of covalent irreversible PI4KIIIB inhibitors for resistance evasion, resolution of the PI4KIIIB crystal structure for the first time, and nomination of up to two lead molecules for in vivo efficacy validation.

Work is performed at Purdue University in West Lafayette, Indiana, with a period of performance from August 21, 2026, through July 31, 2028. The assistance type is a Project Grant (R21 mechanism). The award addresses malaria burden — an estimated 247 million cases worldwide in 2021 resulting in 619,000 deaths — and the critical gap of parasite-mediated drug resistance to all clinically used antimarial therapeutics, including dihydroartemisinin.