On May 22nd, a reporter from Science and Technology Daily learned that Professor Wang Qiaoping's team from the School of Pharmacy of Sun Yat sen University (Shenzhen) and Professor Wan Guohui's team from the School of Pharmacy of Sun Yat sen University have found a potential new therapeutic drug for deadly mushroom poisoning caused by Amanita. The relevant research results are published in the international academic journal Nature Communications. Poisonous goose paste mushrooms grow in a low-key manner, and at first glance they look quite similar to ordinary non-toxic mushrooms, so they are easily ingested by mistake. Poisonous goose paste fungus, also known as "poisonous umbrella", produces highly toxic ingredients“ α- Amanitine (AMA). α- The lethal dose of Amanitine to humans can be as low as 0.1 mg/kg, while a single toxic Amanitine α- The content of Amanita mushroom alkaloids is as high as 15 milligrams, which means that ingesting a poisonous Amanita mushroom by mistake is enough to cause the death of an adult strong man. Goose mushroom alkaloid poisoning can cause a series of symptoms such as acute liver injury. Currently, the main clinical treatment methods include gastric lavage, emesis induction, and non-specific drug treatment. Due to the unclear toxicological mechanism, there is currently a lack of specific detoxifying drugs. "Wang Qiaoping introduced. In response, Wang Qiaoping stated that the research team has adopted a research strategy that combines whole genome CRISPR screening technology and virtual drug screening technology, and has discovered a diagnostic reagent, indocyanine green, which has the potential to treat toxic Amanita poisoning. We use genome-wide CRISPR screening technology to identify protein targets for drug development α- Amanitine tests gene knockout cell libraries to identify cells that can survive under the pressure of toxins after specific genes are knocked out, and enriches the DNA of these surviving cells for sequencing. Further bioinformatics analysis is used to identify the genes and signals required for toxins to kill cells Wang Qiaoping said. The research team found that the STT3B protein and its glycoprotein modification pathway play a crucial role in α- The cytotoxicity of Amanitine is crucial. N-glycan synthesis inhibitor and STT3B knockout can effectively alleviate α- Cytotoxicity of Amanitine. Then, the research team began to develop STT3B inhibitors, used molecular docking technology to virtual screening the drug molecular library approved by the US Food and Drug Administration (FDA), and found 34 potential STT3B inhibitors. Later, they performed in vitro Functional verification on these candidate drugs in cells and found that indocyanine green (ICG) can effectively prevent α- The cell death induced by Amanitine reduces the damage of toxins to liver like organs in mice. Finally, the research team validated the therapeutic effect of indocyanine green through mouse experiments. They injected mice with a certain amount of α- Amanita alkaloids were then treated with indocyanine green at different time points, and it was found that after injection α- Injecting indocyanine green 1 to 4 hours after the use of Amanita alkaloids can effectively alleviate the toxic symptoms in mice. Wang Qiaoping cautiously stated that it is currently uncertain whether indocyanine green has similar effects in humans, which requires more clinical evidence. (Outlook New Era Network)
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Source：http://digitalpaper.stdaily.com/http_www.kjrb.com/kjrb/html/2023-05/24/content_553629.htm?div=-1
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