Project Grant R01AI196477

Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $3.1 million Project Grant to the University of Arizona under the Allergy and Infectious Diseases Research program (CFDA 93.855) for a four-year period commencing June 5, 2026 and concluding May 31, 2030. The grant funds research to identify and characterize novel antifungal compounds targeting dihydroorotate dehydrogenase (DHODH) in Cryptococcus neoformans and Cryptococcus gattii, major fungal pathogens responsible for cryptococcal meningitis with mortality rates exceeding 50% despite current treatments. The research addresses a critical therapeutic gap identified by the World Health Organization, which has designated C. neoformans as one of the four highest priority fungal pathogens due to increasing drug resistance and limited therapeutic options.

The project will employ high-throughput screening (HTS) of large compound libraries to identify selective DHODH inhibitors, followed by iterative medicinal chemistry optimization to improve pharmacokinetics, potency, and selectivity against human DHODH. Identified compounds will be validated for antifungal activity against C. neoformans and other clinically relevant pathogens, with structural studies conducted to characterize the molecular mechanisms of inhibition. This research initiative supports the development of next-generation antifungal therapeutics to address unmet clinical needs in treating cryptococcal infections, particularly in immunocompromised populations.