Influence of EGCG oxidation on inhibitory activity against the SARS-CoV-2 main protease

文献类型： 外文期刊

第一作者： He, Yufeng

作者： He, Yufeng;Hao, Meng;Yang, Mingchuan;Guo, Huimin;Zhang, Jinsong;Guo, Huimin;Rayman, Margaret P.;Zhang, Xiangchun

作者机构：

关键词： SARS-CoV-2 main protease; EGCG; Thiol

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：7.7； 五年影响因子：7.7 ）

ISSN： 0141-8130

年卷期： 2024 年 274 卷

页码：

收录情况： SCI

摘要： SARS-CoV-2 main protease (Mpro) is a well -recognized target for COVID-19 therapy. Green tea (-)-epigallocatechin-3-gallate (EGCG) possesses Mpro-inhibitory activity; however, the influence of EGCG oxidation on its inhibition activity remains obscure, given its high oxidation propensity. This study reveals that prolonged EGCG oxidation in the presence of Mpro dramatically increases its inhibitory activity with an IC 50 of 0.26 mu M. The inhibitory mechanism is that EGCG-quinone preferentially binds the active site Mpro-Cys145-SH, which forms a quinoprotein. Though Mpro is present in the cell lysate, EGCG preferentially depletes its thiols. Noncytotoxic EGCG effectively generates a quinoprotein in living cells, thus EGCG might selectively inhibit Mpro in SARS-CoV-2 infected cells. Chlorogenic acid facilitates EGCG oxidation. Together, they synergistically deplete multiple Mpro thiols though this is not more beneficial than EGCG alone. By contrast, excessive EGCG oxidation prior to incubation with Mpro largely compromises its inhibitory activity. Overall, the low IC 50 and the high selectivity imply that EGCG is a promising dietary Mpro inhibitor. While EGCG oxidation in the presence of Mpro has a pivotal role in inhibition, enhancing EGCG oxidation by chlorogenic acid no longer increases its inhibitory potential. EGCG oxidation in the absence of Mpro should be avoided to maximize its Mpro-inhibitory activity.

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