Researchers from the University of Illinois Urbana-Champaign and the University of Wisconsin-Madison have developed a new antifungal molecule that has the potential to effectively kill fungi without causing toxicity in human cells. The molecule is based on the structure of the well-known antifungal drug Amphotericin B, which is currently used as a last resort treatment for fungal infections. While Amphotericin B is highly effective against fungi, it also has toxic effects on human cells, particularly the kidneys.
Fungal infections are a growing public health concern, and the researchers aimed to find a way to harness the power of Amphotericin B without its associated toxicity. Through their research, they discovered that Amphotericin B kills fungi by extracting ergosterol from fungal cells. However, they also found that it has a similar effect on human kidney cells by extracting cholesterol. To address this issue, the researchers modified Amphotericin B to reduce its interaction with cholesterol, thus minimizing its toxicity.
Using solid-state nuclear magnetic resonance imaging and molecular synthesis techniques, the researchers were able to determine the atomic-level structure of the modified molecule and its binding properties with ergosterol and cholesterol. Armed with this knowledge, they synthesized and tested derivatives of the molecule, eventually identifying one, called AM-2-19, that exhibited potent antifungal properties without toxicity.
AM-2-19 was tested in vitro assays, cell cultures, and live mice, demonstrating broad-spectrum efficacy against over 500 different clinically relevant pathogen species. The molecule also showed high efficacy in mouse models of three common fungal infections.
The researchers believe that AM-2-19 has great potential as a safe and effective antifungal treatment, and it has recently entered Phase 1 clinical trials. If successful, it could offer a promising alternative to current antifungal drugs. However, further clinical studies are needed to assess its effectiveness in humans.
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