Repurposing neurokinin 1 inhibitors for treatment of multidrug-resistant invasive fungal infections

The National Institute of Allergy and Infectious Diseases awarded Virginia Polytechnic Institute & State University $198,695 on June 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to support early-stage translational research on repurposing neurokinin-1 (NK1) receptor antagonists as novel antifungal agents.

The research addresses the growing challenge of multidrug-resistant invasive fungal infections, particularly Candida auris, Aspergillus fumigatus, and Mucorales species. Current therapeutic options are limited to three main antifungal drug classes—azoles, polyenes, and echinocandins—with widespread resistance emerging among fungal pathogens. The project will establish NK1 inhibitors as a new therapeutic strategy, synthesize chemical analogs, and optimize their safety and pharmacokinetic properties to develop novel antifungal treatments.

Work is performed in Blacksburg, Virginia, with a period of performance from June 1, 2026, through May 31, 2028. This is a Project Grant, the primary assistance type for investigator-initiated research in the NIH portfolio.

Abstract

The management of invasive fungal infections remains a significant challenge due to the limited arsenal of antifungal drugs and the growing resistance among fungal pathogens. Currently, only three main classes of antifungal agents (azoles, polyenes, and echinocandins) are used to treat these infections. Resistance to azoles has become alarmingly prevalent among fungal pathogens. While AMB is effective against most fungal pathogens, its clinical application is hampered by severe side effects and dose-limiting toxicity. Alarmingly, approximately 30% of the emerging fungal isolates, candida auris, exhibit resistance to AMB and certain fungal pathogens are intrinsically resistant to echinocandins, further narrowing therapeutic options. The discovery of novel antifungal drugs remains very difficult, emphasizing the need for innovative strategies to combat drug resistance. This proposal outlines a milestone-driven, early-stage translational research project focused on the discovery and development of novel therapeutics targeting select fungal pathogens, including candida auris, aspergillus fumigatus, and mucorales. Specifically, the research aims to explore the potential of neurokinin-1 (NK1) receptor antagonists as antifungal agents. This work aims to establish NK1 inhibitors, synthesize chemical analogs, optimize their safety and pharmacokinetic properties as novel antifungal therapies, offering a promising solution for the treatment of life-threatening fungal infections while addressing the pressing issue of antifungal resistance.