If approved, synthetic compound could bolster shaky arsenal of antifungal drugs.
The antifungal Amphotericin B (AmB) is an old and effective drug—it saved many COVID-19 patients whose compromised immune systems failed to stop secondary fungal infections. But it sometimes causes life-threatening kidney damage. Now, after more than a decade of sleuthing into this toxicity, researchers have not only found an explanation, but used it to devise a powerful antifungal alternative without any obvious side effects in mice and human cells. And the strategy that led to the discovery of the compound, described today in Nature, may offer a route for detoxifying other antimicrobial drugs.
“This is really inspiring work,” says Leah Cowen, a mycologist at the University of Toronto. “They leveraged molecular insights into how the drug works to dial up the properties they wanted and dial down properties they didn’t want.”
Worldwide, fungal diseases kill some 1.5 million people annually, about the same as tuberculosis or malaria. But in contrast with antibiotics, where dozens of classes of effective drugs are available, there are only three classes of antifungals, and each faces problems of toxicity, growing resistance, or limited effectiveness. “We are very much in need of new antifungals that are safe and effective,” Cowen says.
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