Study Finds That A Phytochemical Found In Green Tea Called Epigallocatechin Gallate Exhibits Anti-SARS-CoV-2 Properties Even In New Variants!
Researchers from Temple University Lewis Katz School of Medicine, Philadelphia-USA, Jinan University, Guangzhou-China, University of Nebraska-Lincoln- and the University of Alabama at Birmingham School of Medicine-USA have in a new in vitro study found that the phytochemical called Epigal
locatechin Gallate that is found in green tea exhibits anti-SARS-CoV-2 properties even in new Variants of Concern (VOCs).
While the COVID-19 pandemic rages on, various new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Hence, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARSCoV-2 and its variant infection.
The study team demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG.
It was found that among the four active green tea catechins at noncytotoxic doses, Epigallocatechin Gallate or EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection.
Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells.
The study findings warrants further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for the prevention and treatment of SARS-CoV-2 transmission and infection.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2021.03.17.435637v1
Further compounding to its long list of health benefits, this new research confirms antiviral activity from green tea. One of its ingredients, epigallocatechin gallate (EGCG), blocked the SARS-CoV-2 from binding to human angiotensin-converting enzyme 2 (ACE2) receptors and can subsequently prevent infection of human lung cells.
Most importantly this action was also observed in the SARS-CoV-2 variants of concern (VOC).
At present green tea is one of the most consumed beverages in many countries across East Asia. It has high anti-inflammatory and anti-oxidative properties that could help reduce the risk of developing severe COVID-19 symptoms.
Corresponding author, Dr Wenzhe Ho from the department of Pathology and Laboratory Medicine, Center for Metabolic Disease Research, and Department of Neurology, Temple University Lewis Katz School of Medicine, Philadelphia commented, “Taken together, our data indicate the possibility that consumption of green tea or its active ingredient EGCG is beneficial for preventing or reducing SARS-CoV-2 transmission and infection…Given its low toxicity, anti-inflammation, antioxidant, and anti-SARS-CoV-2 variant properties, use of GTB or EGCG is likely to minimize the SARS-CoV-2 spread, ameliorate symptoms and disease severity.”
The study team created several pseudoviruses that contained S proteins with a single mutation (K417N, E484K, N501Y, D614G) or with full-set mutations of the newly emerged variants (B.1.1.7, B.1.351, and B.1.429).
The team then transfected the pseudoviruses into HEK293T-hACE2 cells. The wild-type S or D614G S was able to cause infection as observed by increased luciferase activity.
The transfected cells showed little cytotoxicity to green tea beverages, indicating it was safe to use.
Importantly green tea effectively prevented infection from the wild-type SARS-CoV-2 or D614G and the COVID-19 variants B.1.429 found in California and B.1.351 found in South Africa — in a dose-dependent manner.
The study team also found green tea beverages prevented other coronaviruses’ infection as observed when tested against HCoV OC43 in HCT-8 cells.
The team next looked to see what was in green tea that was causing these antiviral effects. Catechins ie EGCG, EGC, ECG, and EC were studied because they are green tea’s active ingredients.
The study findings showed three catechins: EGCG, EGC, and ECG, dose-dependently blocked a pseudovirus infection caused by the wild-type SARS-CoV-2 strain.
However upon closer inspection, the study team deduced EGCG as the most potent inhibitor for viral infection. EGCG makes up more than 50% of catechins found in green tea beverages.
In addition, exposing EGCG to mutated strains such as D614G, K417N, E484K, and N501Y suppressed their ability to cause infection.
The study team also found EGCG inhibited viral infection of cells containing variants of concern, including B.1.17, B.1.351, and B.1.429.
Epigallocatechin Gallate or EGCG was tested on infected human lung epithelial cells, where they discovered it could suppress SARS-CoV-2 before and after infection. Although, the inhibitory activity was greater when cells were pretreated with EGCG before SARS-CoV-2 infection.
while catechin’s antiviral activity was also effective in preventing infection from other related coronaviruses, EGCG was the most effective in suppressing HCoV OC43, while EC was the least effective.
It was found that Epigallocatechin Gallate prevents inhibition by blocking SARS-CoV-2 binding to ACE2 receptor.
Epigallocatechin Gallate was most effective in stopping the viral entry of SARS-CoV-2 in human cells before infection although it was also somewhat effective during infection.
The study team found it blocked viral entry by preventing the S1 subunit which has the highest binding affinity to ACE2.
EGCG also decreased binding of the S2 subunit, although it already had a little binding affinity to ACE2.
Dr Wenzhe Ho concluded, “The study found that the recombinant RBD could bind to ACE2 with EC50 of 4.08 ng/mL, while EGCG significantly decreased the binding affinity of RBD (4.7-fold) with EC50 of 19.19 ng/mL. In addition, EGCG also diminished the binding affinity of full-length S to ACE2 by 2.5-fold (EC50: 43.48 to 107.6 ng/mL). The inhibitory effect of EGCG on RBD or full-length S binding to ACE2 was dose-dependent.”
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