1887

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and more than a million deaths. The infection causes COVID-19, a disease of the respiratory system of divergent severity. No treatment exists. Epigallocatechin-3-gallate (EGCG), the major component of green tea, has several beneficial properties, including antiviral activities. Therefore, we examined whether EGCG has antiviral activity against SARS-CoV-2. EGCG blocked not only the entry of SARS-CoV-2, but also MERS- and SARS-CoV pseudotyped lentiviral vectors and inhibited virus infections . Mechanistically, inhibition of the SARS-CoV-2 spike–receptor interaction was observed. Thus, EGCG might be suitable for use as a lead structure to develop more effective anti-COVID-19 drugs.

Funding
This study was supported by the:
  • Deutsches Zentrum für Infektionsforschung (Award TTU 01.802)
    • Principle Award Recipient: MichaelD. Mühlebach
  • Bundesministerium für Gesundheit (Award CHARIS 6a)
    • Principle Award Recipient: S SchnierleBarbara
  • Bundesministerium für Gesundheit (Award CHARIS 6b)
    • Principle Award Recipient: MichaelD. Mühlebach
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. The Microbiology Society waived the open access fees for this article.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001574
2021-04-08
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/102/4/jgv001574.html?itemId=/content/journal/jgv/10.1099/jgv.0.001574&mimeType=html&fmt=ahah

References

  1. Nagle DG, Ferreira D, Zhou Y-D. Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives. Phytochemistry 2006; 67:1849–1855 [View Article]
    [Google Scholar]
  2. Yamaguchi K, Honda M, Ikigai H, Hara Y, Shimamura T. Inhibitory effects of (−)-epigallocatechin gallate on the life cycle of human immunodeficiency virus type 1 (HIV-1). Antiviral Res 2002; 53:19–34 [View Article]
    [Google Scholar]
  3. Fassina G, Buffa A, Benelli R, Varnier OE, Noonan DM et al. Polyphenolic antioxidant (–)-epigallocatechin-3-gallate from green tea as a candidate anti-HIV agent. AIDS 2002; 16:939–941 [View Article]
    [Google Scholar]
  4. Williamson M, McCormick T, Nance C, Shearer W. Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: potential for HIV-1 therapy. J Allergy Clin Immunol 2006; 118:1369–1374 [View Article]
    [Google Scholar]
  5. Kim M, Kim S-Y, Lee HW, Shin JS, Kim P et al. Inhibition of influenza virus internalization by (−)-epigallocatechin-3-gallate. Antiviral Res 2013; 100:460–472 [View Article]
    [Google Scholar]
  6. Ciesek S, von Hahn T, Colpitts CC, Schang LM, Friesland M et al. The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry. Hepatology 2011; 54:1947–1955 [View Article]
    [Google Scholar]
  7. Calland N, Albecka A, Belouzard S, Wychowski C, Duverlie G et al. (−)-Epigallocatechin-3-gallate is a new inhibitor of hepatitis C virus entry. Hepatology 2012; 55:720–729 [View Article]
    [Google Scholar]
  8. Chen C, Qiu H, Gong J, Liu Q, Xiao H. Epigallocatechin-3-gallate inhibits the replication cycle of hepatitis C virus, Arch . Virol 2012; 157:1301–1312
    [Google Scholar]
  9. Colpitts CC, Schang LM. A small molecule inhibits virion attachment to heparan sulfate- or sialic acid-containing glycans. J Virol 2014; 88:7806–7817 [View Article]
    [Google Scholar]
  10. Weber C, Sliva K, von Rhein C, Kümmerer BM, Schnierle BS. The green tea catechin, epigallocatechin gallate inhibits Chikungunya virus infection. Antiviral Res 2015; 113:1–3 [View Article]
    [Google Scholar]
  11. Steinmann J, Buer J, Pietschmann T, Steinmann E. Anti-infective properties of epigallocatechin-3-gallate (EGCG), a component of green tea, Br . J.Pharmacol 2013; 168:1059–1073
    [Google Scholar]
  12. Xu J, Xu Z, Zheng W. A review of the antiviral role of green tea catechins. Molecules 2017; 22:
    [Google Scholar]
  13. Wu F, Zhao S, Yu B, Chen Y-M, Wang W et al. A new coronavirus associated with human respiratory disease in China. Nature 2020; 579:265–269 [View Article]
    [Google Scholar]
  14. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19). JAMA 2020; 324:782–793 [View Article]
    [Google Scholar]
  15. Petersen E, Koopmans M, Go U, Hamer DH, Petrosillo N et al. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect Dis 2020; 20:e238–e244 [View Article]
    [Google Scholar]
  16. Cui J, Li F, Shi Z-L. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; 17:181–192 [View Article]
    [Google Scholar]
  17. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in the treatment of patients infected with 2019-New coronavirus (SARS-CoV-2): a review and perspective. Int J Biol Sci 2020; 16:1708–1717 [View Article]
    [Google Scholar]
  18. Li C, Wang L, Ren L. Antiviral mechanisms of candidate chemical medicines and traditional Chinese medicines for SARS-CoV-2 infection. Virus Res 2020; 286:198073 [View Article]
    [Google Scholar]
  19. Huang J, Tao G, Liu J, Cai J, Huang Z et al. Current prevention of COVID-19: natural products and herbal medicine. Front Pharmacol 2020; 11:588508 [View Article]
    [Google Scholar]
  20. Glowacka I, Bertram S, Herzog P, Pfefferle S, Steffen I et al. Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63. J Virol 2010; 84:1198–1205 [View Article]
    [Google Scholar]
  21. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus ADME, Fouchier RAM. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012; 367:1814–1820 [View Article]
    [Google Scholar]
  22. Drosten C, Günther S, Preiser W, van der Werf S, Brodt H-R et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 2003; 348:1967–1976 [View Article]
    [Google Scholar]
  23. Henss L, Yue C, Kandler J, Faddy HM, Simmons G et al. Establishment of an alphavirus-specific neutralization assay to distinguish infections with different members of the Semliki Forest complex. Viruses 2019; 11:pii:E82 [View Article]
    [Google Scholar]
  24. Grehan K, Ferrara F, Temperton N. An optimised method for the production of MERS-CoV spike expressing viral pseudotypes. MethodsX 2015; 2:379–384 [View Article]
    [Google Scholar]
  25. Henss L, Scholz T, von RC, Wieters I, Borgans F. Analysis of humoral immune responses in SARS-CoV-2 infected patients. J Infect Dis 2020
    [Google Scholar]
  26. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M et al. A third-generation lentivirus vector with a conditional packaging system. J Virol 1998; 72:8463–8471 [View Article]
    [Google Scholar]
  27. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill 2020; 25: [View Article]
    [Google Scholar]
  28. Hörner C, Schürmann C, Auste A, Ebenig A, Muraleedharan S. A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine. Proc Natl Acad Sci USA 2020202014468
    [Google Scholar]
  29. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181:271–280 [View Article]
    [Google Scholar]
  30. Wang C, Li W, Drabek D, Okba NMA, van Haperen R et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun 2020; 11:2251 [View Article]
    [Google Scholar]
  31. Chi X, Yan R, Zhang J, Zhang G, Zhang Y et al. A neutralizing human antibody binds to the N-terminal domain of the spike protein of SARS-CoV-2. Science 2020; 369:650–655 [View Article]
    [Google Scholar]
  32. Schmidt F, Weisblum Y, Muecksch F, Hoffmann H-H, Michailidis E et al. Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses. J Exp Med 2020; 217: [View Article]
    [Google Scholar]
  33. Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G et al. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med Overseas Ed 2020; 382:970–971 [View Article]
    [Google Scholar]
  34. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020; 581:465–469 [View Article]
    [Google Scholar]
  35. Scheuplein VA, Seifried J, Malczyk AH, Miller L, Höcker L et al. High secretion of interferons by human plasmacytoid dendritic cells upon recognition of middle East respiratory syndrome coronavirus. J Virol 2015; 89:3859–3869 [View Article]
    [Google Scholar]
  36. Singh BN, Shankar S, Srivastava RK. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol 2011; 82:1807–1821 [View Article]
    [Google Scholar]
  37. Gan R-Y, Li H-B, Sui Z-Q, Corke H. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): an updated review. Crit Rev Food Sci Nutr 2018; 58:924–941 [View Article]
    [Google Scholar]
  38. Koehler M, Delguste M, Sieben C, Gillet L, Alsteens D. Initial step of virus entry: virion binding to cell-surface glycans. Annu Rev Virol 2020; 7:143–165 [View Article]
    [Google Scholar]
  39. Clausen TM, Sandoval DR, Spliid CB, Pihl J, Perrett HR et al. SARS-CoV-2 infection depends on cellular heparan sulfate and ACE2. Cell 2020; 183:e151043–1057 [View Article][PubMed]
    [Google Scholar]
  40. Wang Z-Y, Li Y-Q, Guo Z-W, Zhou X-H, Lu M-D et al. ERK1/2-HNF4α axis is involved in epigallocatechin-3-gallate inhibition of HBV replication. Acta Pharmacol Sin 2020; 41:278–285 [View Article][PubMed]
    [Google Scholar]
  41. He W, Li L-X LQ-J, Liu C-L, Chen X-L. Epigallocatechin gallate inhibits HBV DNA synthesis in a viral replication - inducible cell line. WJG 2011; 17:1507–1514 [View Article]
    [Google Scholar]
  42. Zhong L, Hu J, Shu W, Gao B, Xiong S. Epigallocatechin-3-gallate opposes HBV-induced incomplete autophagy by enhancing lysosomal acidification, which is unfavorable for HBV replication. Cell Death Dis 2015; 6:e1770 [View Article]
    [Google Scholar]
  43. Huang H-C, Tao M-H, Hung T-M, Chen J-C, Lin Z-J et al. (−)-Epigallocatechin-3-gallate inhibits entry of hepatitis B virus into hepatocytes. Antiviral Res 2014; 111:100–111 [View Article]
    [Google Scholar]
  44. Liu S, Li H, Chen L, Yang L, Li L et al. (-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus spontaneous lytic infection involves ERK1/2 and PI3-K/Akt signaling in EBV-positive cells. Carcinogenesis 2013; 34:627–637 [View Article]
    [Google Scholar]
  45. Chen Y-L, Tsai H-L, Peng C-W. EGCG debilitates the persistence of EBV latency by reducing the DNA binding potency of nuclear antigen 1. Biochem Biophys Res Commun 2012; 417:1093–1099 [View Article]
    [Google Scholar]
  46. Upadhyay S, Tripathi PK, Singh M, Raghavendhar S, Bhardwaj M. Evaluation of medicinal herbs as a potential therapeutic option against SARS-CoV-2 targeting its main protease. Phytother Res 2020
    [Google Scholar]
  47. Chiou W-C, Chen J-C, Chen Y-T, Yang J-M, Hwang L-H et al. The inhibitory effects of PGG and EGCG against the SARS-CoV-2 3C-like protease. Biochem Biophys Res Commun 2021; 382: [View Article]
    [Google Scholar]
  48. Menegazzi M, Campagnari R, Bertoldi M, Crupi R, Di Paola R et al. Protective effect of epigallocatechin-3-gallate (EGCG) in diseases with uncontrolled immune activation: could such a scenario be helpful to counteract COVID-19?. Int J Mol Sci 2020; 21:5171 [View Article]
    [Google Scholar]
  49. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med 2020
    [Google Scholar]
  50. Lee M-J, Maliakal P, Chen L, Meng X, Bondoc FY. Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev 2002; 11:1025–1032
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001574
Loading
/content/journal/jgv/10.1099/jgv.0.001574
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error