Potential protective mechanisms of green tea polyphenol EGCG against COVID-19

Background: The world is in the midst of the COVID-19 pandemic. In this comprehensive review, we discuss the potential protective effects of (-)-epigallocatechin-3-gallate (EGCG), a major constituent of green tea, against COVID-19. Scope and approach: Information from literature of clinical symptoms and molecular pathology of COVID-19 as well as relevant publications in which EGCG shows potential protective activities against COVID-19 is integrated and evaluated. Key findings and conclusions: EGCG, via activating Nrf2, can suppress ACE2 (a cellular receptor for SARS-CoV-2) and TMPRSS2, which mediate cell entry of the virus. Through inhibition of SARS-CoV-2 main protease, EGCG may inhibit viral reproduction. EGCG via its broad antioxidant activity may protect against SARS-CoV-2 evoked mitochondrial ROS (which promote SARS-CoV-2 replication) and against ROS burst inflicted by neutrophil extracellular traps. By suppressing ER-resident GRP78 activity and expression, EGCG can potentially inhibit SARS-CoV-2 life cycle. EGCG also shows protective effects against 1) cytokine storm-associated acute lung injury/acute respiratory distress syndrome, 2) thrombosis via suppressing tissue factors and activating platelets, 3) sepsis by inactivating redox-sensitive HMGB1, and 4) lung fibrosis through augmenting Nrf2 and suppressing NF-kappa B. These activities remain to be further substantiated in animals and humans. The possible concerted actions of EGCG suggest the importance of further studies on the prevention and treatment of COVID-19 in humans. These results also call for epidemiological studies on potential preventive effects of green tea drinking on COVID19.