Project Grant R01AI199984

Duke University's Office of Research Administration received a $824,451 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded June 15, 2026, with a completion date of May 31, 2031. The research focuses on elucidating the molecular mechanisms of action and resistance of FDA-approved antifungal drugs—specifically echinocandins and ibrexafungerp (IBX)—that target fungal beta-(1,3)-glucan synthase. The project involves developing high-resolution cryo-electron microscopy (cryo-EM) structures, functional assays, and computational methods to understand how these antifungals inhibit the glucan synthase enzyme complex and how fungal resistance develops.

The research deliverables include structural characterization of glucan synthase in complex with echinocandin drugs, identification of precise drug binding sites and inhibition mechanisms, analysis of resistance mechanisms emerging from widespread clinical use, and development of functional and computational tools to support antifungal drug research. This fundamental research aims to address the significant public health challenge posed by invasive Candida infections—the second leading cause of hospital-acquired bloodstream infections in the United States—by providing molecular-level insights that can inform the development of improved therapeutics and strategies to combat emerging antifungal resistance.