Novel Antifungal Formulation
An antifungal drug formulation that targets components critical to cell wall biosynthesis.
With the rapid emergence of resistance among fungal species, there is a significant need for new approaches to combating fungal infections. The vast majority of approved antifungal agents are directed at targets involving the cell membrane, though some act on intracellular targets. With the exception of echinocandins, which are glucan synthase inhibitors, the historic approaches represented by classes such as azoles and polyenes overlook fungi’s first line of defense, the cell wall, and, because of their limited set of targets, have contributed to the antifungal resistance crisis we now face.
The novel drug formulation provided here attacks targets critical to cell wall biosynthesis. Mutants possessing knockouts of these targets demonstrated significantly decreased biofilm formation in the presence of ampicillin as compared to their wild-type counterparts, suggesting reduced antibiotic resistance potential. Research has shown that attacking these targets not only affects biofilm formation but also leads to defects in the formation of hyphae, which are known to play a critical role in nutrient absorption and have been linked to virulence, specifically adhesion and invasion of host cells. This formulation has demonstrated promising antifungal effects, with in vitro data showing a decrease of about 6.0E+6 viable cells when compared to the control. Further, one of the components of the drug formulation, MY001, alone has demonstrated hyphae inhibition in vitro with little to no germ tube formation as compared to the control. The second component, MY002, has demonstrated chitin synthase suppression when administered alone. Like the echnocandins and enfumafungin, this cell wall-active formulation offers a promising tool to add to the antifungal drug arsenal.
Through an inhibition of enzymes critical to cell wall biosynthesis, the antifungal formulation provided here may be less susceptible to antifungal resistance. Further, the agents that comprise this formulation appear to pose little, if any, toxicity risk.
- Therapeutic (human and veterinary)
US Provisional Patent Application 62/936,160 filed November 15, 2019.
Demonstration in vitro.
Available for licensing or collaboration.