Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?

Menegazzi, Marta; Campagnari, Rachele; Bertoldi, Mariarita; Crupi, Rosalia; Paola, Rosanna Di; Cuzzocrea, Salvatore

doi:10.3390/ijms21145171

Cited by 85 publications

(58 citation statements)

References 131 publications

(176 reference statements)

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“…6 ). These herbs contain flavonoids (myricetin from litchi chinensis seed) ( 44 ), flavan-3-ol (catechin and epigallocatechin gallate from tea and Spatholobus root) ( 45 , 46 ), caffeic acid derivatives [caftaric acid and chlorogenic acid ( 47 ) from purple coneflower or honeysuckle flower bud or chia seed ( 48 )] ( SI Appendix , Fig. S2 ), and whether they are related to the antiviral activity remains to be investigated.…”

Section: Resultsmentioning

confidence: 99%

Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection

Jan

Cheng

Juang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

151

152

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The outbreak of COVID-19 caused by SARS-CoV-2 has resulted in more than 50 million confirmed cases and over 1 million deaths worldwide as of November 2020. Currently, there are no effective antivirals approved by the Food and Drug Administration to contain this pandemic except the antiviral agent remdesivir. In addition, the trimeric spike protein on the viral surface is highly glycosylated and almost 200,000 variants with mutations at more than 1,000 positions in its 1,273 amino acid sequence were reported, posing a major challenge in the development of antibodies and vaccines. It is therefore urgently needed to have alternative and timely treatments for the disease. In this study, we used a cell-based infection assay to screen more than 3,000 agents used in humans and animals, including 2,855 small molecules and 190 traditional herbal medicines, and identified 15 active small molecules in concentrations ranging from 0.1 nM to 50 μM. Two enzymatic assays, along with molecular modeling, were then developed to confirm those targeting the virus 3CL protease and the RNA-dependent RNA polymerase. Several water extracts of herbal medicines were active in the cell-based assay and could be further developed as plant-derived anti–SARS-CoV-2 agents. Some of the active compounds identified in the screen were further tested in vivo, and it was found that mefloquine, nelfinavir, and extracts of Ganoderma lucidum (RF3), Perilla frutescens, and Mentha haplocalyx were effective in a challenge study using hamsters as disease model.

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Section: Resultsmentioning

confidence: 99%

Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection

Jan

Cheng

Juang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

151

152

View full text Add to dashboard Cite

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“…In this aspect, EGCG is potentially a promising agent for COVID-19 to revert hyperinflammation. Previous studies have demonstrated that EGCG can strongly inhibit the JAK/STAT pathway regulating the synthesis and secretion of several cytokines and chemokines [ 58 , 59 ]. Moreover, EGCG can suppress the canonical NF-κB pathway [ 60 , 61 ], which plays a key regulatory role in the expression of proinflammatory cytokines including IL-1, TNF-α, IL8, IL-6.…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2

Zheng

Disoma

et al. 2021

International Journal of Biological Macromolecules

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SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued. Here, we report that epigallocatechin-3-gallate (EGCG), an active ingredient of Chinese herbal medicine (CHM), is a potent inhibitor of 3CLpro with half-maximum inhibitory concentration (IC50) of 0.874 ± 0.005 μM. In the study, we retrospectively analyzed the clinical data of 123 cases of COVID-19 patients, and found three effective Traditional Chinese Medicines (TCM) prescriptions. Multiple strategies were performed to screen potent inhibitors of SARS-CoV-2 3CLpro from the active ingredients of TCMs, including network pharmacology, molecular docking, surface plasmon resonance (SPR) binding assay and fluorescence resonance energy transfer (FRET)-based inhibition assay. The SPR assay showed good interaction between EGCG and 3CLpro with KD ~6.17 μM, suggesting a relatively high affinity of EGCG with SARS-CoV-2 3CLpro. Our results provide critical insights into the mechanism of action of EGCG as a potential therapeutic agent against COVID-19.

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“…Besides, EGCG is protective in diseases with uncontrolled immune activation, thus, may ameliorate severity of COVID-19 13 since the latter is related to overreaction of the immune system. 14 Altogether these results suggest that green tea catechins could reduce overall risks related to COVID-19.…”

Section: Introductionmentioning

confidence: 99%

COVID -19: could green tea catechins reduce the risks?

Storozhuk

2020

Preprint

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Objectives: Several lines of emerging pharmacological and epidemiological evidence imply that overall risks related to COVID-19 may be reduced by green tea catechins. Therefore, it may be expected that: (i) higher green tea consumption is associated with lower COVID-19 morbidity and/or mortality; (ii) countries with higher per/capita green tea consumption would be less affected by COVID-19. The aim of this study was to assess the second possibility. Study design: This was a cross-sectional study. Methods: Among countries with at least 3 million population (n=134), countries with relatively high (above 150 g) per/capita green tea consumption have been tentatively identified (n=21); (ii) normalized to population values of COVID-19 cases (morbidity) and deaths (mortality) for groups of countries with high and low per/capita green tea consumption were compared. Results: Striking differences in COVID-19 morbidity (and mortality) between groups of countries with higher and lower green tea consumption. The differences were still observed after the adjustment for the onset of the disease. Besides, preliminary analysis using multiple linear regression approach suggests that the associations are present at the level of individual countries. Conclusion: Evidence supporting the idea that green tea constituents could reduce overall risks related to COVID-19 has been obtained. The results are promising and are in line with emerging evidence from other studies including pharmacological ones. Nevertheless, because of limitations of this study the idea still should be considered as a hypothesis requiring further assessment.

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Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?

Cited by 85 publications

References 131 publications

Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection

Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection

Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2

COVID -19: could green tea catechins reduce the risks?

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