Tea catechins in green tea inhibit the activity of the SARS-CoV-2 main protease via covalent adduction

Yoji Kato; Sakiko Suzuki; Akari Higashiyama; Ichiro Kaneko; Mitsugu Akagawa; Miyu Nishikawa; Shinichi Ikushiro

doi:10.51094/jxiv.897

##article.authors##

Yoji Kato School of Human Science and Environment, University of Hyogo
Sakiko Suzuki School of Human Science and Environment, University of Hyogo
Akari Higashiyama School of Human Science and Environment, University of Hyogo
Ichiro Kaneko School of Human Science and Environment, University of Hyogo
Mitsugu Akagawa Department of Food and Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
Miyu Nishikawa Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University
Shinichi Ikushiro Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University

DOI:

https://doi.org/10.51094/jxiv.897

Keywords:

coronavirus main protease, green tea, catechins, pyrogallol, intracellular reaction

Abstract

Here, we examined the inhibitory effects of tea catechins on the SARS-CoV-2 main protease (M^pro). Among the eight catechins examined, epigallocatechin 3-(3′′-O-methyl)gallate (EGCG3′′Me), epigallocatechin gallate (EGCG), gallocatechin, gallocatechin gallate, and epigallocatechin inhibited the recombinant M^pro enzyme in a dose-dependent manner. Covalent binding of catechins to M^pro was confirmed by quinone staining and intact mass spectrometry. Peptide mapping revealed the preferential covalent adduction of catechin to the active site sequence of M^pro. Fragmentation analysis revealed 184 liberations from the digested peptides, corresponding to monomethylated gallic acid (D ring) liberation, indicating that the B‑ring was bound to the active site. When 10 bottled teas were incubated with M^pro, the green teas inhibited the enzyme, whereas the blended and barley tea did not. EGCG covalently reacted with the viral enzyme intracellularly on incubation with cultured cells expressing coronavirus M^pro, suggesting that the catechins in green tea can inhibit M^pro in infected cells.

Conflicts of Interest Disclosure

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Author Biography

Yoji Kato, School of Human Science and Environment, University of Hyogo

School of Human Science and Environment, University of Hyogo

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