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Drug Discovery

Scientists find possible antidote for death cap mushroom poisoning

Indocyanine green identified using genome-wide CRISPR study and virtual drug screening

by Bethany Halford
May 16, 2023

 

Structure of indocyanine green.

Amanita phalloides, also known as the death cap mushroom, contains the toxin α-amanitin, which causes irreparable liver and kidney damage. While this type of mushroom poisoning is rare in the US, it accounted for 788 deaths in China from 2010–2020, according to a study of China’s Foodborne Disease Outbreaks Surveillance System. There are treatments for α-amanitin poisoning, such as silibinin, but their mechanisms of action aren’t well understood.

Scientists led by Guohui Wan and Qiaoping Wang at Sun Yat-sen University wanted to understand how α-amanitin kills cells and possibly discover an antidote. Using genome-wide CRISPR screening, they found that a protein called STT3B is required for α-amanitin toxicity.

The researchers then virtually screened a library of more than 3,000 FDA-approved compounds to find one that could block STT3B. In molecular docking simulations, they found that indocyanine green—a dye used to determine heart and liver function—could slip into the entrance STT3B’s substrate-binding pocket. Indocyanine green prevented α-amanitin toxicity in cells and liver organoids and also helped mice survive α-amanitin poisoning if given within 4 h of the poison (Nat. Commun. 2023, DOI: 10.1038/s41467-023-37714-3).

“Further research is necessary to ascertain whether it possesses the same therapeutic benefits in human subjects,” Wang says in an email. But if it’s successful, he says indocyanine green “could represent a groundbreaking, life-saving treatment for individuals suffering from mushroom poisoning.”

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