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Identification of indocyanine green as a STT3B inhibitor against mushroom α-amanitin cytotoxicity

Authors :
Bei Wang
Arabella H. Wan
Yu Xu
Ruo-Xin Zhang
Ben-Chi Zhao
Xin-Yuan Zhao
Yan-Chuan Shi
Xiaolei Zhang
Yongbo Xue
Yong Luo
Yinyue Deng
G. Gregory Neely
Guohui Wan
Qiao-Ping Wang
Source :
Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023)
Publication Year :
2023
Publisher :
Nature Portfolio, 2023.

Abstract

Abstract The “death cap”, Amanita phalloides, is the world’s most poisonous mushroom, responsible for 90% of mushroom-related fatalities. The most fatal component of the death cap is α-amanitin. Despite its lethal effect, the exact mechanisms of how α-amanitin poisons humans remain unclear, leading to no specific antidote available for treatment. Here we show that STT3B is required for α-amanitin toxicity and its inhibitor, indocyanine green (ICG), can be used as a specific antidote. By combining a genome-wide CRISPR screen with an in silico drug screening and in vivo functional validation, we discover that N-glycan biosynthesis pathway and its key component, STT3B, play a crucial role in α-amanitin toxicity and that ICG is a STT3B inhibitor. Furthermore, we demonstrate that ICG is effective in blocking the toxic effect of α-amanitin in cells, liver organoids, and male mice, resulting in an overall increase in animal survival. Together, by combining a genome-wide CRISPR screen for α-amanitin toxicity with an in silico drug screen and functional validation in vivo, our study highlights ICG as a STT3B inhibitor against the mushroom toxin.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
14
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.661b392320124b23b3e5ae286e7a1fce
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-023-37714-3