Therapeutic potential of green tea catechin, (-)-epigallocatechin-3-O-gallate (EGCG) in SARS-CoV-2 infection: Major interactions with host/virus proteases

• Published in: Phytomedicine Plus : International journal of phytotherapy and phytopharmacology 2023-02, Vol.3 (1), p.100402, Article 100402
• Main Authors: Dinda, Biswanath, Dinda, Subhajit, Dinda, Manikarna
• Format: Article
• Language: English
• Subjects: COVID-19; Epigallocatechin-3-O-gallate; Green tea; Host/viral proteases inhibitor; SARS-CoV-2
• ISSN: 2667-0313; 2667-0313
• DOI: 10.1016/j.phyplu.2022.100402

•EGCG inhibits the binding of SARS-CoV-2 spike (S) protein with host ACE2 receptor.•EGCG promotes Nrf2 activation for suppression of ACE2 and TMPRSS2 expression and activity in host cells.•EGCG in vitro prevents SARS-CoV-2 replication and infection in host cells by inhibiting the activities of 3CLpro, PLpro, Nsp15, and RdRp.•EGCG prevents virus-induced cytokine storm, HMGB1 secretion, lung fibrosis and thrombosis-like complications in host cells. The current COVID-19 pandemic from the human pathogenic virus SARS-CoV-2 has resulted in a major health hazard globally. The morbidity and transmission modality of this disease are severe and uncontrollable. As no effective clinical drugs are available for treatment of COVID-19 infection till to date and only vaccination is used as prophylaxis and its efficacy is restricted due to emergent of new variants of SARS-CoV-2, there is an urgent need for effective drugs for its treatment. The aim of this review was to provide a detailed analysis of anti-SARS-CoV-2 efficacy of (-)-epigallocatechin-3-O-gallate (EGCG), a major catechin constituent of green tea (Camellia sinensis (L.) Kuntze) beverage to highlight the scope of EGCG in clinical medicine as both prophylaxis and treatment of present COVID-19 infection. In addition, the factors related to poor oral bioavailabilty of EGCG was also analysed for a suggestion for future research in this direction. We collected the published articles related to anti-SARS-CoV-2 activity of EGCG against the original strain (Wuhan type) and its newly emerged variants of SARS-CoV-2 virus. A systematic search on the published literature was conducted in various databases including Google Scholar, PubMed, Science Direct and Scopus to collect the relevant literature. The findings of this search demonstrate that EGCG shows potent antiviral activity against SARS-CoV-2 virus by preventing viral entry and replication in host cells in vitro models. The studies on the molecular mechanisms of EGCG in inhibition of SARS-CoV-2 infection in host cells reveal that EGCG blocks the entry of the virus particles by interaction with the receptor binding domain (RBD) of viral spike (S) protein to host cell surface receptor protease angiotensin-converting enzyme 2 (ACE2) as well as suppression of the expressions of host proteases, ACE2, TMPRSS2 and GRP78, required for viral entry, by Nrf2 activation in host cells. Moreover, EGCG inhibits the activities of SARS-CoV-2 main protease (Mpro), papain-like protease