Researchers in the Hong Lab, in collaboration with the Heitman Lab (Department of Molecular Genetics and Microbiology) and the Steinbach and Juvvadi Labs (University of Arkansas), have announced a significant advancement in the fight against fungal infections. They have developed a series of new antifungal drugs that show potent activity against harmful fungi while minimizing effects on the human immune system. Fungal infections pose a significant global health threat, but there are limited treatment options available. Current antifungal drugs often have undesirable side effects, which can be caused by a variety of factors including interactions with the human body's own systems. This new research focuses on a different approach, targeting a specific complex called calcineurin-FKBP12 that is crucial for fungal survival. The research team used advanced techniques, including analysis of crystal structures and computer-aided design, to create modified versions of FK520, a natural product targeting calcineurin-FKBP12 with known antifungal properties. These new derivatives demonstrated strong antifungal activity while significantly reducing the unwanted immunosuppressive effects. The researchers' work, titled "Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi" has been published in the Proceedings of the National Academy of Sciences (PNAS). This finding has the potential to revolutionize the treatment of fungal infections and improve global health.
