Tea catechins in green tea inhibit the activity of the SARS-CoV-2 main protease via covalent adduction
DOI:
https://doi.org/10.51094/jxiv.897キーワード:
coronavirus main protease、 green tea、 catechins、 pyrogallol、 intracellular reaction抄録
Here, we examined the inhibitory effects of tea catechins on the SARS-CoV-2 main protease (Mpro). Among the eight catechins examined, epigallocatechin 3-(3′′-O-methyl)gallate (EGCG3′′Me), epigallocatechin gallate (EGCG), gallocatechin, gallocatechin gallate, and epigallocatechin inhibited the recombinant Mpro enzyme in a dose-dependent manner. Covalent binding of catechins to Mpro was confirmed by quinone staining and intact mass spectrometry. Peptide mapping revealed the preferential covalent adduction of catechin to the active site sequence of Mpro. 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 Mpro, 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 Mpro, suggesting that the catechins in green tea can inhibit Mpro in infected cells.利益相反に関する開示
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.ダウンロード *前日までの集計結果を表示します
引用文献
Bahun, M., Jukić, M., Oblak, D., Kranjc, L., Bajc, G., Butala, M., . . . Poklar Ulrih, N. (2022). Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols. Food Chemistry, 373, 131594. https://doi.org/10.1016/j.foodchem.2021.131594.
Cabrera, C., Artacho, R., & Giménez, R. (2006). Beneficial effects of green tea—A review. J. Am. Nutr. Assoc., 25(2), 79-99. https://doi.org/10.1080/07315724.2006.10719518.
Chauhan, M., Bhardwaj, V. K., Kumar, A., Kumar, V., Kumar, P., Enayathullah, M. G., . . . Kumar, S. (2022). Theaflavin 3-gallate inhibits the main protease (Mpro) of SARS-CoV-2 and reduces its count in vitro. Scientific Reports, 12(1), 13146. https://doi.org/10.1038/s41598-022-17558-5.
Chen, Z., Du, R., Cooper, L., Achi, J. G., Dong, M., Ran, Y., . . . Cui, Q. (2023). Sulforaphane is a reversible covalent inhibitor of 3-chymotrypsin-like protease of SARS-CoV-2. J. Med. Virol., 95(3), e28609. https://doi.org/10.1002/jmv.28609.
Dai, W., Ruan, C., Zhang, Y., Wang, J., Han, J., Shao, Z., . . . Liang, J. (2020). Bioavailability enhancement of EGCG by structural modification and nano-delivery: A review. J. Funct. Foods, 65, 103732. https://doi.org/10.1016/j.jff.2019.103732.
Du, A., Zheng, R., Disoma, C., Li, S., Chen, Z., Li, S., . . . Xia, Z. (2021). Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2. Int. J. Biol. Macromol., 176, 1-12. https://doi.org/10.1016/j.ijbiomac.2021.02.012.
Gerber, P. P., Duncan, L. M., Greenwood, E. J. D., Marelli, S., Naamati, A., Teixeira-Silva, A., . . . Matheson, N. J. (2022). A protease-activatable luminescent biosensor and reporter cell line for authentic SARS-CoV-2 infection. PLOS Pathog., 18(2), e1010265. https://doi.org/10.1371/journal.ppat.1010265.
Hayashi, A., Terasaka, S., Nukada, Y., Kameyama, A., Yamane, M., Shioi, R., . . . Morita, O. (2022). 4″-Sulfation is the major metabolic pathway of epigallocatechin-3-gallate in humans: characterization of metabolites, enzymatic analysis, and pharmacokinetic profiling. J. Agric. Food Chem., 70(27), 8264-8273. https://doi.org/10.1021/acs.jafc.2c02150.
He, Y., Hao, M., Yang, M., Guo, H., Rayman, M. P., Zhang, X., & Zhang, J. (2024). Influence of EGCG oxidation on inhibitory activity against the SARS-CoV-2 main protease. Int J Biol Macromol, 133451. https://doi.org/10.1016/j.ijbiomac.2024.133451.
Hu, Q., Xiong, Y., Zhu, G.-H., Zhang, Y.-N., Zhang, Y.-W., Huang, P., & Ge, G.-B. (2022). The SARS-CoV-2 main protease (Mpro): Structure, function, and emerging therapies for COVID-19. MedComm, 3(3), e151. https://doi.org/10.1002/mco2.151.
Joseph, J., Karthika, T., Das, V. R. A., & Raj, V. S. (2021). Epigallocatechin-3-gallate (EGCG): a potential molecule for the development of therapeutics against emerging SARS-CoV-1, MERS-CoV and SARS-CoV-2 coronaviruses. J Glob Antimicrob Resist, 26, 26-28. https://doi.org/10.1016/j.jgar.2021.05.005.
Kato, Y., Higashiyama, A., Takaoka, E., Nishikawa, M., & Ikushiro, S. (2021). Food phytochemicals, epigallocatechin gallate and myricetin, covalently bind to the active site of the coronavirus main protease in vitro. Adv Redox Res, 3, 100021. https://doi.org/10.1016/j.arres.2021.100021.
Kato, Y., Sakanishi, A., Matsuda, K., Hattori, M., Kaneko, I., Nishikawa, M., & Ikushiro, S. (2023). Covalent adduction of serotonin-derived quinones to the SARS-CoV-2 main protease expressed in a cultured cell. Free Radic Biol Med, 206, 74-82. https://doi.org/10.1016/j.freeradbiomed.2023.06.018.
Kurita, I., Maeda-Yamamoto, M., Tachibana, H., & Kamei, M. (2010). Antihypertensive effect of benifuuki tea containing O-methylated EGCG. J Agric Food Chem, 58(3), 1903-1908. https://doi.org/10.1021/jf904335g.
Liu, J., Bodnar, B. H., Meng, F., Khan, A. I., Wang, X., Saribas, S., . . . Ho, W. (2021). Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor. Cell Biosci, 11(1), 168. https://doi.org/10.1186/s13578-021-00680-8.
Liu, S.-Y., Wang, W., Ke, J.-P., Zhang, P., Chu, G.-X., & Bao, G.-H. (2022). Discovery of Camellia sinensis catechins as SARS-CoV-2 3CL protease inhibitors through molecular docking, intra and extra cellular assays. Phytomedicine, 96, 153853. https://doi.org/10.1016/j.phymed.2021.153853.
Ma, C., Tan, H., Choza, J., Wang, Y., & Wang, J. (2022). Validation and invalidation of SARS-CoV-2 main protease inhibitors using the Flip-GFP and Protease-Glo luciferase assays. Acta Pharmaceutica Sinica B, 12(4), 1636-1651. https://doi.org/https://doi.org/10.1016/j.apsb.2021.10.026.
Manach, C., Williamson, G., Morand, C., Scalbert, A., & Rémésy, C. (2005). Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies2. Am J Clin Nutr, 81(1), 230S-242S. https://doi.org/10.1093/ajcn/81.1.230S.
Marty, M. T., Baldwin, A. J., Marklund, E. G., Hochberg, G. K. A., Benesch, J. L. P., & Robinson, C. V. (2015). Bayesian deconvolution of mass and ion mobility spectra: From binary interactions to polydisperse ensembles. Anal Chem, 87(8), 4370-4376. https://doi.org/10.1021/acs.analchem.5b00140.
Nakayama, M., Suzuki, K., Toda, M., Okubo, S., Hara, Y., & Shimamura, T. (1993). Inhibition of the infectivity of influenza virus by tea polyphenols. Antivr Res, 21(4), 289-299. https://doi.org/10.1016/0166-3542(93)90008-7.
Ngwe Tun, M. M., Luvai, E., Nwe, K. M., Toume, K., Mizukami, S., Hirayama, K., . . . Morita, K. (2022). Anti-SARS-CoV-2 activity of various PET-bottled Japanese green teas and tea compounds in vitro. Arch Virol, 167, 1547-1557. https://doi.org/10.1007/s00705-022-05483-x.
Ohgitani, E., Shin-Ya, M., Ichitani, M., Kobayashi, M., Takihara, T., Kawamoto, M., . . . Mazda, O. (2021a). Rapid inactivation in vitro of SARS-CoV-2 in saliva by black tea and green tea. Pathogens, 10(6), 721. https://doi.org/10.3390/pathogens10060721.
Ohgitani, E., Shin-Ya, M., Ichitani, M., Kobayashi, M., Takihara, T., Kawamoto, M., . . . Mazda, O. (2021b). Significant inactivation of SARS-CoV-2 in vitro by a green tea catechin, a catechin-derivative, and black tea galloylated theaflavins. Molecules, 26(12), 3572. https://doi.org/10.3390/molecules26123572.
Oritani, Y., Setoguchi, Y., Ito, R., Maruki-Uchida, H., Ichiyanagi, T., & Ito, T. (2013). Comparison of (-)-epigallocatechin-3-O-gallate (EGCG) and O-methyl EGCG bioavailability in rats. Biol Pharm Bull, 36(10), 1577-1582. https://doi.org/10.1248/bpb.b13-00349.
Owen, D. R., Allerton, C. M. N., Anderson, A. S., Aschenbrenner, L., Avery, M., Berritt, S., . . . Zhu, Y. (2021). An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19. Science, 374(6575), 1586-1593. https://doi.org/doi:10.1126/science.abl4784.
Paz, M. A., Flückiger, R., Boak, A., Kagan, H. M., & Gallop, P. M. (1991). Specific detection of quinoproteins by redox-cycling staining. J Biol Chem, 266(2), 689-692. https://doi.org/10.1016/S0021-9258(17)35225-0.
Rawson, J. M. O., Duchon, A., Nikolaitchik, O. A., Pathak, V. K., & Hu, W. S. (2021). Development of a cell-based luciferase complementation assay for identification of SARS-CoV-2 3CLpro inhibitors. Viruses, 13(2), 173. https://doi.org/10.3390/v13020173.
Resnick, S. J., Iketani, S., Hong, S. J., Zask, A., Liu, H., Kim, S., . . . Chavez, A. (2021). Inhibitors of coronavirus 3CL proteases protect cells from protease-mediated cytotoxicity. J Virol, 95(14), e0237420. https://doi.org/10.1128/jvi.02374-20.
Rizzuti, B., Grande, F., Conforti, F., Jimenez-Alesanco, A., Ceballos-Laita, L., Ortega-Alarcon, D., . . . Velazquez-Campoy, A. (2021). Rutin is a low micromolar inhibitor of SARS-CoV-2 main protease 3CLpro: Implications for drug design of quercetin analogs. Biomedicines, 9(4), 375. https://doi.org/10.3390/biomedicines9040375.
Rothan, H. A., & Teoh, T. C. (2021). Cell-based high-throughput screening protocol for discovering antiviral inhibitors against SARS-COV-2 main protease (3CLpro). Mol Biotechnol, 63(3), 240-248. https://doi.org/10.1007/s12033-021-00299-7.
Sasaki, M., Tabata, K., Kishimoto, M., Itakura, Y., Kobayashi, H., Ariizumi, T., . . . Sawa, H. (2023). S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters. Sci Transl Med, 15(679), eabq4064. https://doi.org/10.1126/scitranslmed.abq4064.
Song, J.-M., Lee, K.-H., & Seong, B.-L. (2005). Antiviral effect of catechins in green tea on influenza virus. Antivir Resa, 68(2), 66-74. https://doi.org/10.1016/j.antiviral.2005.06.010.
Su, H., Yao, S., Zhao, W., Zhang, Y., Liu, J., Shao, Q., . . . Xu, Y. (2021). Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease. Nat Commun, 12(1), 3623. https://doi.org/10.1038/s41467-021-23751-3.
Tanaka, T., Ishii, T., Mizuno, D., Mori, T., Yamaji, R., Nakamura, Y., . . . Akagawa, M. (2011). (-)-Epigallocatechin-3-gallate suppresses growth of AZ521 human gastric cancer cells by targeting the DEAD-box RNA helicase p68. Free Radic Biol Med, 50(10), 1324-1335. https://doi.org/10.1016/j.freeradbiomed.2011.01.024.
Umeda, D., Yano, S., Yamada, K., & Tachibana, H. (2008). Green tea polyphenol epigallocatechin-3-gallate signaling pathway through 67-kDa laminin receptor. J Biol Chem, 283(6), 3050-3058. https://doi.org/10.1074/jbc.M707892200.
Xiao, T., Cui, M., Zheng, C., Wang, M., Sun, R., Gao, D., . . . Zhou, H. (2021). Myricetin inhibits SARS-CoV-2 viral replication by targeting Mpro and ameliorates pulmonary inflammation. Front Pharmacol, 12, 669642. https://doi.org/10.3389/fphar.2021.669642.
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投稿日時: 2024-09-10 01:48:36 UTC
公開日時: 2024-09-12 01:34:43 UTC
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Copyright(c)2024
Kato, Yoji
Sakiko Suzuki
Akari Higashiyama
Ichiro Kaneko
Mitsugu Akagawa
Miyu Nishikawa
Shinichi Ikushiro
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