Highly efficient discovery of the covalent Mpro inhibitors from crude Pu-erh tea by integrating biochemical and chemoproteomic approaches
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...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Tsinghua University Press
2025-05-01
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| Series: | Food Science and Human Wellness |
| Subjects: | |
| Online Access: | https://www.sciopen.com/article/10.26599/FSHW.2024.9250120 |
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| Summary: | 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. |
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| ISSN: | 2097-0765 2213-4530 |