@article{Zhu2025, 
author = {Guanghao Zhu and Yani Zhang and Shenglan Qi and Jianrong Xu and Yuan Xiong and Zhaoqin Zhang and Xixiang Chen and Yuanyuan Xie and Xiaoqing Guan and Weidong Zhang and Wei Liu and Guangbo Ge},
title = {Highly efficient discovery of the covalent Mpro inhibitors from crude Pu-erh tea by integrating biochemical and chemoproteomic approaches},
year = {2025},
journal = {Food Science and Human Wellness},
volume = {14},
number = {5},
pages = {9250120},
keywords = {Pu-erh tea, Plant extract, Global chemical analysis, Cysteine-modification profiling, Main proteases (Mpro)},
url = {https://www.sciopen.com/article/10.26599/FSHW.2024.9250120},
doi = {10.26599/FSHW.2024.9250120},
abstract = {The main proteases (Mpros) are hydrolases playing essential roles in the replication of β-coronaviruses including SARS-CoV-2. Herein, a highly efficient strategy was developed for discovering the Mpro inactivators from crude plant extract integrating target-based biochemical assay and chemoproteomic approaches. Firstly, Pu-erh tea was found to potently suppress SARS-CoV-2 Mpro in a time-dependent manner. Next, global chemical analysis coupling with peptide-modification profiling were used to identify the cysteine-modified constituents in Pu-erh tea. The results suggested that seven constituents in Pu-erh tea could modify SARS-CoV-2 Mpro, which turned out that epigallocatechin, gallocatechin and gallic acid were the most efficacious Mpro inactivators. Further investigations demonstrated that epigallocatechin and gallocatechin could inactivate SARS-CoV-2 Mpro via blocking the formation of the homodimers. Collectively, this work proposed a novel and practical strategy for highly efficient discovery of time-dependent inhibitors of SARS-CoV-2 Mpro from plant extracts, while 3 constituents in Pu-erh tea have emerged as robust SARS-CoV-2 Mpro inactivators.}
}