Scientists have identified, by testing it on mice, a possible antidote to poisoning with Amanita phalloides, the deadliest poisonous fungus for which there is no cure, according to a study published Tuesday. Antidote name: indocyanine green, a dye used in medical imaging diagnostics. This substance, already authorized by the US drug agency (FDA), could "save many lives", according to Chinese researchers whose work appears in Nature Communications.

Fungal poisoning is the leading cause of death in cases of food poisoning worldwide. In China, 788 deaths from ingestion of poisonous mushrooms were recorded between 2010 and 2020, according to the authors of the study. Amanita phalloides, nicknamed "calyx of death", a white-lamellared fungus often confused with edible species, is responsible for more than 90% of these deaths. Consumption of a single mushroom of the species can prove fatal.

An "unexpected connection"

There is currently no real antidote to phalloidal poisoning, which damages liver and kidneys because the composition of the main toxic constituent of the fungus, alpha-amanitin, is not well known. A team led by a researcher at Sun-Yat-sen University in Guangzhou has tried to target this toxin using CRISPR genetic screening, which helps understand the role of genes in viral infections and poisonings. This same technology had allowed them to find, in 2019, a potential antidote against the deadly bites of box jellyfish, one of the most venomous animals in the world.

The researchers succeeded in identifying the protein, STT3B, which is primarily responsible for the toxicity of Amanita phalloides. They then searched the FDA database for a molecule that could inhibit the offending protein: indocyanine green (ICG). This fluorescent dye is given to patients to be able to visualize certain blood vessels, or determine hepatic blood flow. "This unexpected connection baffled us, and rightly so," Sun Yat-sen University researcher Qiaoping Wang and lead author of the study told AFP.

Soon tests on humans?

The team first tested the antidote on liver cells in petri dishes, then on a mouse. In both cases, the product "demonstrated significant potential in mitigating the toxic effect" of fungus poisoning, the researcher explained. "This molecule has immense potential for the treatment of cases of human poisoning by fungi and could be the very first specific antidote with a targeted protein," he said. If it proves as effective in humans as it is in mice, "it could save many lives."

The team now intends to test the effects of indocyanine green on poisoning in humans. Previous treatments for phalloidal poisoning have been tested, including silybin, an extract of milk thistle, and penicillin, but their mechanisms of action still remain mysterious.

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