{Reference Type}: Journal Article
{Title}: Identification of indocyanine green as a STT3B inhibitor against mushroom α-amanitin cytotoxicity.
{Author}: Wang B;Wan AH;Xu Y;Zhang RX;Zhao BC;Zhao XY;Shi YC;Zhang X;Xue Y;Luo Y;Deng Y;Neely GG;Wan G;Wang QP;
{Journal}: Nat Commun
{Volume}: 14
{Issue}: 1
{Year}: 2023 05 16
{Factor}: 17.694
{DOI}: 10.1038/s41467-023-37714-3
{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.