Description
Objective: This topic is intended for technology proven ready to move directly into Phase II and accepts Direct to Phase II proposals only. The proposed research will focus on identifying compounds with broad-spectrum activity against clinically relevant fungal pathogens while minimizing toxicity to humans. The primary objective is to identify a small molecule with fungicidal properties that are safe for human use, with FDA clearance. Description: Fungal infections represent a growing global health challenge, particularly among immuno-compromised individuals. Invasive fungal infections caused by pathogens such as Candida species, Aspergillus species, Fusarium species, and Mucor species are associated with high morbidity and mortality rates. Fungal infections are associated with 130k hospitalizations, 13 million outpatient visits, and result in a financial burden of $19 billion on the civilian health care sector. Fungal wound infections in particular are also growing challenge for the military. Despite the availability of antifungal agents, current treatments are often limited by toxicity, drug resistance, and narrow-spectrum activity. The emergence of multidrug-resistant fungal strains, such as Candida auris, has further exacerbated the need for novel antifungal therapies. Small molecules with antifungal properties offer a promising avenue for addressing these challenges. Their ability to target specific fungal pathways, combined with the potential for oral bioavailability and low manufacturing costs, makes them ideal candidates for therapeutic development. However, significant scientific and technical hurdles remain with the discovery and optimization of small molecules that are both effective against fungal pathogens and safe for human use. Qualified proposals should identify small molecules with antifungal properties from an existing library. These small molecules should be active against all of the following fungi: Fusarium species, Aspergillus species, Candida auris, or Mucorales species. Qualified molecules will have antifungal activity at nanomolar concentrations. Further, these small molecules must have a cytotoxicity profile similar, or better than Amphotericin B. Keywords: Wounds, infections, fungi, antifungals, antimicrobials, biochemistry, microbiology, mycology CMMC Level: Level 2 (Self)