Introduction
SARS-Cov-2 is a novel coronavirus causing the severe acute respiratory syndrome spreading around the world since the end of 2019.1,2 It belongs to a family of single-stranded RNA viruses (+ssRNA), as the severe acute respiratory syndrome virus (SARS-CoV) and the Middle East respiratory syndrome virus (MERS-CoV). SARS-CoV-2 infection can cause mild to severe pneumonia and its mortality rate is higher in patients with comorbidities and older patients.3,4 Although different vaccines for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have been developed and are now available,5 there are no effective antiviral drugs to treat the disease, except for Remdesivir authorized by the United States Food and Drug Administration (US FDA) to counteract the emergency.6 mRNA-based vaccines were developed by Moderna and Pfizer/BioNTech,7,8 but there is still uncertainty about their efficacy (~95%), safety, and immunogenicity concerning SARS-CoV-2 spike glycoprotein (S protein). Similarly, viral vector vaccines were produced by Johnson and Johnson and by the University of Oxford/AstraZeneca, although the safety of AstraZenecas vaccine is currently under revision.9,10 Unfortunately, new strains of the virus have developed so far with new mutations and this could inhibit the effectiveness of vaccines, and delays the end of the pandemic.11 Given the high infectivity of new mutations in the virus and the slowness of vaccine programming, herd immunity will be difficult to achieve in a short time. It is very likely that new coronavirus diseases may still emerge in the future. Thus, it can be necessary to develop alternative therapies based on the use of natural compounds, as epigallocatechin-3-gallate (EGCG), with antiviral features, to circumvent SARS-CoV-2 infection. EGCG, is the principal constituent and most important polyphenolic catechin found in green tea.1218 As largely reported, EGCG possesses many biological properties (ie antioxidant, antitumor, anti-inflammatory) due to a galloyl side chain contained in its chemical structure.19 It has been shown that polyphenols and EGCG, through sticking with some molecules present in viruses, are able to regulate their functions. Specifically, EGCG by binding to the receptors present on the membrane of the host cells or directly to the viral surface inhibits the interaction between the host cells and the virus. As a result, EGCG represses the replication and the transcription of the virus, thus inactivating its activity.20,21 As recently detailed described by Wang et al,22 EGCG has inhibitory activities towards different viruses. Specifically, EGCG is able to suppress the replication, the transcription and the infection of DNA virus as Hepatitis B Virus (HBV),2327 Herpes Simplex Virus (HSV)2831 and Epstein-Barr Virus (EBV) through different molecular mechanisms.3235 Moreover, EGCG has similar effects on RNA virus as Human Immunodeficiency Virus (HIV),3742 Hepatitis C virus (HCV),4345 and Influenza A virus (IAV).4648 Additionally, in vitro studies demonstrated that EGCG is capable to inhibit the replication of some Enterovirus (CVB3, EV71) by regulating the oxidative stress of host cells.49,50 Similar effects were also detected in Arboviruses, particularly in Chikungunya virus (CHIKV).5155 Finally, several pre-clinical studies confirmed the antiviral activity of EGCG also against Coronaviruses, especially against SARS-Cov-2.5673 Basically, EGCG can inhibit the cell entry of these viruses or their replication and transcription, through different molecular mechanisms which are not completely known. In this review, we summarize these experimental pieces of evidence and highlighted the potential use of EGCG as an alternative therapeutic choice for alleviating or treat SARS-Cov-2 infection.
COVID-19 is caused by SARS-CoV-2 infection.56 The initial clinical manifestations of COVID-19 include respiratory symptoms, such as fever, fatigue and dry cough, are accompanied by atypical clinical manifestations such as sore throat, headache and diarrhea.57 Around one week later, patients exhibited difficulty breathing and hypoxia, during which the secretion of intracellular pro-inflammatory factors Interleukin-6 (IL-6), Interleukin-17 (IL-17) and tumor necrosis factor (TNF-)) increased significantly, and the total number of circulating lymphocytes decreased. Then, the symptoms rapidly deteriorated into acute respiratory distress syndrome (ARDS), sepsis, blood coagulation dysfunction and irreversible metabolic acidosis. Eventually, some severe cases would lead to death. Structurally, SARS-CoV-2 contains four proteins including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. During host cell entry, SARS-CoV-2 relies on its S proteins for binding to the host cell-surface receptor. The S protein binds to the host receptor through the receptor-binding domain (RBD) in the S1 subunit, followed by the fusion of the S2 subunit to the cell membrane. SARS-CoV-2 recognizes the cell membrane receptor angiotensin-converting enzyme 2 (ACE2) receptor to bind with the viral S protein, thus forming RBDACE2 complex, by which the virus is embedded into the host cell where it starts replication. Thus, if a substance can bind the S protein, or possesses a strong affinity to ACE2 receptor, which blocks the formation of RBDACE2 complex, it could suppress the viral entry into host cells. Regarding the antiviral effects of EGCG on SARS-CoV-2, different pre-clinical studies have been performed (Table 1). Basically, the inhibition effects of EGCG on SARS-CoV-2 replication occur through its actions on the ACE2 receptor, the main protease (Mpro, a 3C-like protease) and RNA-dependent RNA polymerase (RdRp) (Figure 1).
Table 1 A Summary of Pre-Clinical Studies on the Antiviral Activity of EGCG Against SARS-Cov-2
Figure 1 The inhibitory effects of EGCG on SARS-CoV-2 life cycle. The figure represents the inhibitory effects of EGCG on SARS-CoV-2 cycle. Basically, the inhibition effects of EGCG on SARS-CoV-2 replication occurs through its actions on the ACE2 receptor, the main protease (Mpro, a 3C-like protease) and RNA-dependent RNA polymerase (RdRp).
Abbreviations: EGCG, epigallocatechin-3-gallate; pp1a, nuclear protein phosphatase 1 ; pp1ab, 2-O-methyltransferase; Mpro, main protease; ACE2, angiotensin-converting enzyme 2; S-protein, spike protein; RdRp, RNA-dependent RNA polymerase.
Mhatre et al58 reviewed the antiviral activities of EGCG theaflavin-3,3-digallate (TF3) against positive-sense single-stranded RNA viruses, including SARS-CoV-2. The authors suggested that both the tea polyphenols are capable to interact with the receptors present in the structure of SARS-CoV-2 virus, thus inhibiting its replication. Particularly, the theaflavins (TFs), can be employed as prophylactic agents due to their capacity to bind Spike receptor-binding domain (RBD), the principal binding domain of the S protein located on the S1 subunit of SARS-CoV-2 virus. EGCG can be used as a potential prophylactic due to its ability to dock to various active sites of SARS-CoV-2 virus. The authors highlighted the needing of additional studies on the specificity, safety, and efficacy of these polyphenols, to confirm their use not only as a dietary supplement, but also as therapeutic agents for COVID-19 infections. Menegazzi et al,59 speculated that EGCG and others catechins (ie, GTE) supplementation could be effective in controlling the inflammation damages occurring in SARS-CoV-2 infection, through complex molecular mechanisms involving different interacting transcriptor factors (ie signal transducer and activator of transcription, STAT; nuclear factor kappa-light-chain-enhancer of activated B cells, NF-B; NF-E2related factor 2; Nuclear Factor Erythroid-Derived 2-Related Factor 2, Nrf2). Similarly, Mendonca et al,60 suggested that the combination of EGCG, thymoquinone (TQ), and vitamin D3 can activate Nrf2-dependent genes and preserve the cells against SARS-CoV-2 infection. Singh et al,61 studied the binding of polyphenols (ie, EGCG, TF1, TF2a, TF2b, hesperidin, quercetagetin, and myricetin) with SARS-CoV-2 RdRp and thus tested their potential to treat COVID-19. The authors demonstrated that EGCG, TF1, TF2a, TF2b, TF3, can bind (in highly stable manner) to the active site of RdRp. These four natural polyphenols can act as potential inhibitors for the SARS-CoV-2 RdRp, although additional studies will be necessary to validate their efficacy against SARS-CoV-2 infection. An in-silico analysis conducted by Sagaama et al,62 revealed that the succinic acid (SA), L-pyroglutamic acid (L-PGA), N-phenyl-thioacetamide (N-NPTA), 2-amino-5-chloropyridine hydrogen succinate (ACPS), epigallocatechine Gallate (EGCG) or, 2-oxoglutarate dehydrogenase E1 component putative (KDH) and, selenomethionine (SeM) compounds could represented potential antiviral candidates for treatment of COVID-19 based on B3LYP/6-311++G** calculations and molecular docking. Data emerged from this study suggest that the compounds ACPS and KDH are powerful species in the treatment of SARS-CoV-2 infections. A different study conducted by Jang et al,63 demonstrated that EGCG and theaflavins, inhibited activity against the SARS-CoV-2 3CL-protease, in HEK293T cells, in a dose-dependent manner and without signs of cytotoxicity for both compounds at any dose used. Sharma et al,64 performed an in-silico drug repurposing followed by molecular dynamics (MD) simulation and MM-GBSA calculation for targeting SARS-CoV-2 main protease (Mpro). Mpro was screened for already known FDA approved drugs and some natural compounds, including EGCG. Specifically, the authors proposed that EGCG, withaferin A, dolutegravir and artesunate could be considered potential drugs for COVID-19. A molecular docking studies was also conducted by Mhatre et al,65 to study the exact interaction of EGCG and TF3 with the putative binding sites of SARS-CoV-2. The in-silico results emerged from this study should promote the evaluation of the broad-spectrum antiviral activity of the tea polyphenols in the treatment of COVID-19. Similarly, Zhu et al66 performed in vitro studies by using of the Mpro of SARS-Cov-2 for docking simulation to screen flavan-3-ols and proanthocyanidins (Pas), to identify potential candidates for counteracting SARS-Cov-2 infection. Data emerged from docking simulation and in vitro assay, indicated that ()-catechin-3-O-gallate (CAG), ()-epicatechin-3-O-gallate (ECG), ()-gallocatechin-3-O-gallate GCG), EGCG, procyanidin A2 (PA2) and B2 (PB2) are able to inhibit the Mpro activity of SARS-Cov-2, thus can be used to interfere with SARS-Cov-2 infection. Wang et al,67 conducted in-depth and comprehensive bioinformatics analysis for the screening of therapeutic drugs and their related pathways in COVID-19 disease. Results indicated that trans-resveratrol, EGCG and BX795 possess multiple anti-viral effects. It is of note that coronaviruses encode for polyproteins that are cleaved by 3CL protease for maturation. Thus, 3CL protease could be considered the main target of antivirals against coronaviruses. Based on this concept, Chiou et al,68 conducted an in vitro study on the inhibitory effects of 1,2,3,4,6-pentagalloylglucose (PGG) and EGCG against the SARS-CoV-2- 3-chymotrypsin-like protease (3CLpro) protease. Data revealed that PGG and EGCG inhibited of viral protease activity of SARS-CoV-2 3CLpro, thus suggesting their potential application in the treatment of SARS-CoV-2 infection. Later on, in a fascinating study Du et al,69 screened and identified, by using multiple strategies (ie molecular docking, surface plasmon resonance, fluorescence resonance energy transfer (FRET)-based inhibition assay) different active ingredients of Traditional Chinese Medicine (TCM) with inhibitory effects against SARS-CoV-2 3CLpro, including EGCG. Results demonstrate that EGCG showed a higher affinity with SARS-CoV-2 3CLpro thus suggesting its potential in the treatment of COVID-19 disease. A fascinating in vitro study performed by Jang et al,70 demonstrated that EGCG can inhibit coronavirus replication. Specifically, the authors used low pathogenic human coronavirus HCoV-OC43 (beta coronavirus) and HCoV-229E (alpha coronavirus), as a coronavirus model system to dissect the effect of EGCG on coronavirus processing. Results demonstrated that EGCG treatment decreases viral RNA and viral protein production in the media suggesting that EGCG inhibits coronavirus replication. By using the molecular docking approach, Chourasia et al71 demonstrated that the catechins (mainly EGCG and ECG) inhibited papain-like protease protein (PLPro). Specifically, catechin bind to the S1 ubiquitin-binding site of PLPro, which restrain its protease function and abolish SARS-CoV-2 inhibitory function on ubiquitin proteasome system and interferon stimulated gene system. Considering EGGCs antiviral and anti-inflammatory properties, the authors concluded that these natural compounds could be considered as a putative therapeutic agent for SARS-CoV-2 infection. Finally, a recent research conducted by Henss et al,72 examined the antiviral activity of EGCG against SARS-CoV-2. EGCG arrested the entry of SARS-CoV-2, MERS and SARS-CoV pseudo typed lentiviral vectors and restrained virus infections in vitro. Moreover, an inhibition of the SARS-CoV-2 spikereceptor interaction was also detected. Altogether these finding highlighted the potential use of EGCG as an alternative therapeutic choice for the treatment of SARS-CoV-2 infection.
Here, we summarized recent findings on the potential role of EGCG in the treatment of SARS-CoV-2 infection. Accumulated pieces of evidence reported that EGCG has antiviral properties against different viruses, including SARS-Cov-2.22 Specifically, it has been proved that EGCG inhibits the enzymatic activity of the coronavirus 3CL protease, thus interfering with its replication. Moreover, EGCG can regulate specific target as the viral S protein and RdRp. EGCG is also capable of inhibiting the replication of coronaviruses in cell cultures. Results from molecular docking analyses demonstrated that EGCG prevents SARS-CoV-2 entry into the target cell through inhibition of RBD in viral membrane identifying with ACE2. Finally, EGCG can interfere with the viral start replication by suppressing Mpro activity, although all these effects should be confirmed in vivo. A set of experiments evaluated the in vivo distribution of EGCG in human bodies7479 and data showed that the values of EGCG concentration in the colon and intestine were higher than most of the concentrations necessary to promote 3CL protease required to effectively 3CL protease inhibition. More pre-clinical studies, clinical trials and epidemiological analysis will be extremely needed to validate EGCG anti-COVID-19 applications. EGCG and its stable lipophilic derivatives could also be potential prophylactic as well as therapeutic agents looking at their properties to dock at various active sites of SARS-CoV-2. Results from these studies will shed light on the role of the EGCG and the underlying molecular mechanisms for the treatment of SARS-CoV-2 infection. However, based on the current results published in the literature, it is not possible to say at all that EGCG can be considered as an election therapeutic drug for Covid-19. Due to the absence of specificity, EGCG could bind to other proteins present in the human body, thus provoking side-effects. EGGC may not be used in the treatment of COVID-19, but as a nutraceutical or dietary supplement, especially in the earlier stages of clinical manifestations of COVID-19. After extensive studies on EGGC and other similar polyphenols regarding their specificity, activity, bioavailability and safety, there can be considerations on their use in the treatment of viral infections including COVID-19.
We are grateful to Dr. Alessandra Trocino and Mrs. Cristina Romano from the National Cancer Institute of Naples for providing excellent bibliographic service and assistance. Sabrina Bimonte and Cira Antonietta Forte are co-first authors of this study. Marco Cascella and Arturo Cuomo are co-last authors of this study.
All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval for the version to be published, and agree to be accountable for all aspects of the work.
The authors report no conflicts of interest in this work.
1. Bimonte S, Crispo A, Amore A, Celentano E, Cuomo A, Cascella M. Potential antiviral drugs for SARS-Cov-2 treatment: preclinical findings and ongoing clinical research. In vivo. 2020;34(3 Suppl):15971602. doi:10.21873/invivo.11949
2. Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265269. doi:10.1038/s41586-020-2008-3
3. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782793. doi:10.1001/jama.2020.12839
4. Petersen E, Koopmans M, Go U, et al. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect Dis. 2020;20(9):e238e244. doi:10.1016/S1473-3099(20)30484-9
5. Nagy A, Alhatlani B. An overview of current COVID-19 vaccine platforms. Comput Struct Biotechnol J. 2021;19:25082517. doi:10.1016/j.csbj.2021.04.061
6. Vitiello A, Ferrara F, Porta R. Remdesivir and COVID-19 infection, therapeutic benefits or unnecessary risks? Ir J Med Sci. 2021;12. doi:10.1007/s11845-020-02482-2
7. Baden LR, El Sahly HM, Essink B, et al.; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403416. doi:10.1056/NEJMoa2035389
8. Xia X. Domains and functions of spike protein in Sars-Cov-2 in the context of vaccine design. Viruses. 2021;13(1):109. doi:10.3390/v13010109
9. Bjrnstad-Tuveng TH, Rudjord A, Anker P. Fatal cerebral haemorrhage after COVID-19 vaccine. Tidsskr nor Laegeforen. 2021;141. English, Norwegian. doi:10.4045/tidsskr.21.0312
10. Maas DPMSM, Kramers C, Smit HJCA, Middeldorp S, Helsloot I. Prikpauze AstraZeneca proportioneel? [Temporary suspension of AstraZenecas vaccine; a reconstruction]. Ned Tijdschr Geneeskd. 2021;165:D6065. Dutch.
11. CDC Emerging Sars-Cov-2 Variants. Available from: https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html#. Accessed January 28, 2021.
12. Bimonte S, Cascella M. The potential roles of epigallocatechin-3-gallate in the treatment of ovarian cancer: current state of knowledge. Drug Des Devel Ther. 2020;14:42454250. doi:10.2147/DDDT.S253092
13. Bimonte S, Cascella M, Barbieri A, Arra C, Cuomo A. Current shreds of evidence on the anticancer role of EGCG in triple negative breast cancer: an update of the current state of knowledge. Infect Agent Cancer. 2020;15:2. doi:10.1186/s13027-020-0270-5
14. Bimonte S, Cascella M, Barbieri A, Arra C, Cuomo A. Shining a light on the effects of the combination of (-)-epigallocatechin-3-gallate and tapentadol on the growth of human triple-negative breast cancer cells. In Vivo. 2019;33(5):14631468. doi:10.21873/invivo.11625
15. Bimonte S, Albino V, Piccirillo M, et al. Epigallocatechin-3-gallate in the prevention and treatment of hepatocellular carcinoma: experimental findings and translational perspectives. Drug Des Devel Ther. 2019;13:611621. doi:10.2147/DDDT.S180079
16. Cascella M, Bimonte S, Muzio MR, Schiavone V, Cuomo A. The efficacy of Epigallocatechin-3-gallate (green tea) in the treatment of Alzheimers disease: an overview of pre-clinical studies and translational perspectives in clinical practice. Infect Agent Cancer. 2017;12:36. doi:10.1186/s13027-017-0145-6
17. Bimonte S, Cascella M, Leongito M, et al. An overview of pre-clinical studies on the effects of (-)-epigallocatechin-3-gallate, a catechin found in green tea, in treatment of pancreatic cancer. Recenti Prog Med. 2017;108(6):282287. doi:10.1701/2715.27715
18. Bimonte S, Leongito M, Barbieri A, et al. Inhibitory effect of (-)-epigallocatechin-3-gallate and bleomycin on human pancreatic cancer MiaPaca-2 cell growth. Infect Agent Cancer. 2015;10:22. doi:10.1186/s13027-015-0016-y
19. Nagle DG, Ferreira D, Zhou YD. Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives. Phytochemistry. 2006;67(17):18491855. doi:10.1016/j.phytochem.2006.06.020
20. Xu J, Xu Z, Zheng W. A review of the antiviral role of green tea catechins. Molecules. 2017;22(8):1337. doi:10.3390/molecules22081337
21. 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(5):10591073. doi:10.1111/bph.12009
22. Wang YQ, Li QS, Zheng XQ, Lu JL, Liang YR. Antiviral effects of green tea EGCG and its potential application against COVID-19. Molecules. 2021;26(13):3962. doi:10.3390/molecules26133962
23. Xu J, Gu W, Li C, et al. Epigallocatechin gallate inhibits hepatitis B virus via farnesoid X receptor alpha. J Nat Med. 2016;70(3):584591. doi:10.1007/s11418-016-0980-6
24. 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(5):e1770. doi:10.1038/cddis.2015.136
25. Pang JY, Zhao KJ, Wang JB, Ma ZJ, Xiao XH. Green tea polyphenol, epigallocatechin-3-gallate, possesses the antiviral activity necessary to fight against the hepatitis B virus replication in vitro. J Zhejiang Univ Sci B. 2014;15(6):533539. doi:10.1631/jzus.B1300307
26. Chen M, Sllberg M, Hughes J, et al. Immune tolerance split between hepatitis B virus precore and core proteins. J Virol. 2005;79(5):30163027. doi:10.1128/JVI.79.5.3016-3027.2005
27. He W, Li LX, Liao QJ, Liu CL, Chen XL. Epigallocatechin gallate inhibits HBV DNA synthesis in a viral replication - inducible cell line. World J Gastroenterol. 2011;17(11):15071514. doi:10.3748/wjg.v17.i11.1507
28. Haberichter J, Roberts S, Abbasi I, Dedthanou P, Pradhan P, Nguyen ML. The telomerase inhibitor MST-312 interferes with multiple steps in the herpes simplex virus life cycle. J Virol. 2015;89(19):98049816. doi:10.1128/JVI.01006-15
29. Isaacs CE, Wen GY, Xu W, et al. Epigallocatechin gallate inactivates clinical isolates of herpes simplex virus. Antimicrob Agents Chemother. 2008;52(3):962970. doi:10.1128/AAC.00825-07
30. Gosslau A, En Jao DL, Huang MT, et al. Effects of the black tea polyphenol theaflavin-2 on apoptotic and inflammatory pathways in vitro and in vivo. Mol Nutr Food Res. 2011;55(2):198208. doi:10.1002/mnfr.201000165
31. Pradhan P, Nguyen ML. Herpes simplex virus virucidal activity of MST-312 and epigallocatechin gallate. Virus Res. 2018;249:9398. doi:10.1016/j.virusres.2018.03.015
32. Kutok JL, Wang F. Spectrum of Epstein-Barr virus-associated diseases. Annu Rev Pathol. 2006;1:375404. doi:10.1146/annurev.pathol.1.110304.100209
33. Lo YM. Quantitative analysis of Epstein-Barr virus DNA in plasma and serum: applications to tumor detection and monitoring. Ann N Y Acad Sci. 2001;945:6872. doi:10.1111/j.1749-6632.2001.tb03865.x
34. Chang LK, Wei TT, Chiu YF, et al. Inhibition of Epstein-Barr virus lytic cycle by (-)-epigallocatechin gallate. Biochem Biophys Res Commun. 2003;301(4):10621068. doi:10.1016/s0006-291x(03)00067-6
35. Liu S, Li H, Chen 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(3):627637. doi:10.1093/carcin/bgs364
36. Hamza A, Zhan CG. How can (-)-epigallocatechin gallate from green tea prevent HIV-1 infection? Mechanistic insights from computational modeling and the implication for rational design of anti-HIV-1 entry inhibitors. J Phys Chem B. 2006;110(6):29102917. doi:10.1021/jp0550762
37. Zhang HS, Wu TC, Sang WW, Ruan Z. EGCG inhibits Tat-induced LTR transactivation: role of Nrf2, AKT, AMPK signaling pathway. Life Sci. 2012;90(1920):747754. doi:10.1016/j.lfs.2012.03.013
38. Williamson MP, McCormick TG, Nance CL, Shearer WT. 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(6):13691374. doi:10.1016/j.jaci.2006.08.016
39. Castellano LM, Hammond RM, Holmes VM, Weissman D, Shorter J. Epigallocatechin-3-gallate rapidly remodels PAP85-120, SEM1(45107), and SEM2(49107) seminal amyloid fibrils. Biol Open. 2015;4(9):12061212. doi:10.1242/bio.010215
40. Duan JM, Qiu JY, Tan SY, Liu SW, Li L. [Semen-derived enhancer of viral infectiona key factor in sexual transmission of HIV]. Bing Du Xue Bao. 2012;28(1):8488. Chinese.
41. Hauber I, Hohenberg H, Holstermann B, Hunstein W, Hauber J. The main green tea polyphenol epigallocatechin-3-gallate counteracts semen-mediated enhancement of HIV infection. Proc Natl Acad Sci U S A. 2009;106(22):90339038. doi:10.1073/pnas.0811827106
42. Li S, Hattori T, Kodama EN. Epigallocatechin gallate inhibits the HIV reverse transcription step. Antivir Chem Chemother. 2011;21(6):239243. doi:10.3851/IMP1774
43. Liu S, Lu H, Zhao Q, et al. Theaflavin derivatives in black tea and catechin derivatives in green tea inhibit HIV-1 entry by targeting gp41. Biochim Biophys Acta. 2005;1723(13):270281. doi:10.1016/j.bbagen.2005.02.012
44. Wang YF, Shao SH, Xu P, Yang XQ, Qian LS. Catechin-enriched green tea extract as a safe and effective agent for antimicrobial and anti-inflammatory treatment. Afr J Pharm Pharmacol. 2011;5:14521461. doi:10.5897/AJPP11.164
45. Kuzuhara T, Iwai Y, Takahashi H, Hatakeyama D, Echigo N. Green tea catechins inhibit the endonuclease activity of influenza A virus RNA polymerase. PLoS Curr. 2009;1:RRN1052. doi:10.1371/currents.rrn1052
46. Kim M, Kim SY, Lee HW, et al. Inhibition of influenza virus internalization by (-)-epigallocatechin-3-gallate. Antiviral Res. 2013;100(2):460472. doi:10.1016/j.antiviral.2013.08.002
47. Ling JX, Wei F, Li N, et al. Amelioration of influenza virus-induced reactive oxygen species formation by epigallocatechin gallate derived from green tea. Acta Pharmacol Sin. 2012;33(12):15331541. doi:10.1038/aps.2012.80
48. Song JM, Lee KH, Seong BL. Antiviral effect of catechins in green tea on influenza virus. Antiviral Res. 2005;68(2):6674. doi:10.1016/j.antiviral.2005.06.010
49. He X, Gao B, Zhou L, Xiong S. Green tea polyphenol epigallocatechin-3-gallate-alleviated coxsackievirus B3-induced myocarditis through inhibiting viral replication but not through inhibiting inflammatory responses. J Cardiovasc Pharmacol. 2017;69(1):4147. doi:10.1097/FJC.0000000000000439
50. Ho HY, Cheng ML, Weng SF, Leu YL, Chiu DT. Antiviral effect of epigallocatechin gallate on enterovirus 71. J Agric Food Chem. 2009;57(14):61406147. doi:10.1021/jf901128u
51. Carneiro BM, Batista MN, Braga ACS, Nogueira ML, Rahal P. The green tea molecule EGCG inhibits Zika virus entry. Virology. 2016;496:215218. doi:10.1016/j.virol.2016.06.012
52. Weber C, Sliva K, von Rhein C, Kmmerer BM, Schnierle BS. The green tea catechin, epigallocatechin gallate inhibits chikungunya virus infection. Antiviral Res. 2015;113:13. doi:10.1016/j.antiviral.2014.11.001
53. Lu JW, Hsieh PS, Lin CC, et al. Synergistic effects of combination treatment using EGCG and suramin against the chikungunya virus. Biochem Biophys Res Commun. 2017;491(3):595602. doi:10.1016/j.bbrc.2017.07.157
54. Vazquez-Calvo , Jimnez de Oya N, Martn-Acebes MA, Garcia-Moruno E, Saiz JC. Antiviral properties of the natural polyphenols delphinidin and epigallocatechin gallate against the flaviviruses West Nile virus, Zika virus, and Dengue virus. Front Microbiol. 2017;8:1314. doi:10.3389/fmicb.2017.01314
55. Su S, Wong G, Shi W, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016;24(6):490502. doi:10.1016/j.tim.2016.03.003
56. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270273. doi:10.1038/s41586-020-2012-7
57. Weiss SR, Navas-Martin S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev. 2005;69(4):635664. doi:10.1128/MMBR.69.4.635-664.2005
58. Mhatre S, Srivastava T, Naik S, Patravale V. Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: a review. Phytomedicine. 2021;85:153286. doi:10.1016/j.phymed.2020.153286
59. Menegazzi M, Campagnari R, Bertoldi M, Crupi R, Di Paola R, Cuzzocrea S. 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(14):5171. doi:10.3390/ijms21145171
60. Mendonca P, Soliman KFA. Flavonoids activation of the transcription factor Nrf2 as a hypothesis approach for the prevention and modulation of SARS-CoV-2 infection severity. Antioxidants. 2020;9(8):659. doi:10.3390/antiox9080659
61. Singh S, Sk MF, Sonawane A, Kar P, Sadhukhan S. Plant-derived natural polyphenols as potential antiviral drugs against SARS-CoV-2 via RNA-dependent RNA polymerase (RdRp) inhibition: an in-silico analysis. J Biomol Struct Dyn. 2020;28:116. doi:10.1080/07391102.2020.1796810
62. Sagaama A, Brandan SA, Ben Issa T, Issaoui N. Searching potential antiviral candidates for the treatment of the 2019 novel coronavirus based on DFT calculations and molecular docking. Heliyon. 2020;6(8):e04640. doi:10.1016/j.heliyon.2020.e04640
63. Jang M, Park YI, Cha YE, et al. Tea polyphenols EGCG and theaflavin inhibit the activity of SARS-CoV-2 3CL-protease in vitro. Evid Based Complement Alternat Med. 2020;2020:5630838. doi:10.1155/2020/5630838
64. Sharma S, Deep S. In-silico drug repurposing for targeting SARS-CoV-2 main protease (Mpro). J Biomol Struct Dyn. 2020;12:18. doi:10.1080/07391102.2020.1844058
65. Mhatre S, Naik S, Patravale V. A molecular docking study of EGCG and theaflavin digallate with the druggable targets of SARS-CoV-2. Comput Biol Med. 2021;129:104137. doi:10.1016/j.compbiomed.2020.104137
66. Zhu Y, Xie DY. Docking characterization and in vitro inhibitory activity of flavan-3-ols and dimeric proanthocyanidins against the main protease activity of SARS-Cov-2. Front Plant Sci. 2020;11:601316. doi:10.3389/fpls.2020.601316
67. Wang T, Zhao M, Ye P, Wang Q, Zhao Y. Integrated bioinformatics analysis for the screening of associated pathways and therapeutic drugs in coronavirus disease 2019. Arch Med Res. 2021;52(3):304310. doi:10.1016/j.arcmed.2020.11.009
68. Chiou WC, Chen JC, Chen YT, et al. The inhibitory effects of PGG and EGCG against the SARS-CoV-2 3C-like protease. Biochem Biophys Res Commun. 2021. doi:10.1016/j.bbrc.2020.12.106
69. Du A, Zheng R, Disoma C, et al. Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2. Int J Biol Macromol. 2021;176:112. doi:10.1016/j.ijbiomac.2021.02.012
70. Jang M, Park R, Park YI, et al. EGCG, a green tea polyphenol, inhibits human coronavirus replication in vitro. Biochem Biophys Res Commun. 2021;547:2328. doi:10.1016/j.bbrc.2021.02.016
71. Chourasia M, Koppula PR, Battu A, Ouseph MM, Singh AK. EGCG, a green tea catechin, as a potential therapeutic agent for symptomatic and asymptomatic SARS-CoV-2 infection. Molecules. 2021;26(5):1200. doi:10.3390/molecules26051200
72. Henss L, Auste A, Schrmann C, et al. The green tea catechin epigallocatechin gallate inhibits SARS-CoV-2 infection. J Gen Virol. 2021;102(4):001574. doi:10.1099/jgv.0.001574
73. Park J, Park R, Jang M, Park YI. Therapeutic potential of EGCG, a green tea polyphenol, for treatment of coronavirus diseases. Life. 2021;11(3):197. doi:10.3390/life11030197
74. Lambert JD, Lee MJ, Lu H, et al. Epigallocatechin-3-gallate is absorbed but extensively glucuronidated following oral administration to mice. J Nutr. 2003;133(12):41724177. doi:10.1093/jn/133.12.4172
75. Nakagawa K, Miyazawa T. Absorption and distribution of tea catechin, (-)-epigallocatechin-3-gallate, in the rat. J Nutr Sci Vitaminol. 1997;43(6):679684. doi:10.3177/jnsv.43.679
76. Hollman PC, Tijburg LB, Yang CS. Bioavailability of flavonoids from tea. Crit Rev Food Sci Nutr. 1997;37(8):719738. doi:10.1080/10408399709527799
77. Yang CS, Lee MJ, Chen L. Human salivary tea catechin levels and catechin esterase activities: implication in human cancer prevention studies. Cancer Epidemiol Biomarkers Prev. 1999;8(1):8389.
78. Li Y, Ren B, Peng X, et al. Saliva is a non-negligible factor in the spread of COVID-19. Mol Oral Microbiol. 2020;35(4):141145. doi:10.1111/omi.12289
79. Ohgitani E, Shin-Ya M, Ichitani M, et al. Rapid inactivation in vitro of SARS-CoV-2 in saliva by black tea and green tea. Pathogens. 2021;10(6):721. doi:10.3390/pathogens10060721
See more here:
Potential roles of EGCG in the treatment of COVID-19 | DDDT - Dove Medical Press
- Understanding Menopause and its Symptoms | Menopause Treatment Options - Medriva - December 28th, 2023 [December 28th, 2023]
- Breast cancer survivor Jayne Pritchard talks alternative therapies over tea - MidlandToday - December 28th, 2023 [December 28th, 2023]
- 12 unusual ways Israelis are volunteering during the war - ISRAEL21c - December 28th, 2023 [December 28th, 2023]
- Complementary and alternative medicine - NHS - December 26th, 2022 [December 26th, 2022]
- Alternative Treatment (CAM) for MS: Types, Side Effects & Cost - December 26th, 2022 [December 26th, 2022]
- Complementary and alternative medicine | History & Facts - December 26th, 2022 [December 26th, 2022]
- Alternative medicine: Definition, examples, benefits, and risks - October 28th, 2022 [October 28th, 2022]
- Alternative Medicine: The Science Behind 10 Alternative Therapies - October 21st, 2022 [October 21st, 2022]
- Detoxification (alternative medicine) - Wikipedia - October 21st, 2022 [October 21st, 2022]
- Alternative Approaches to Mental Health and Wellbeing - Psychiatric Times - October 19th, 2022 [October 19th, 2022]
- New practice focuses on dental sleep medicine, providing an alternative for patients who use CPAP machines - PennLive - October 19th, 2022 [October 19th, 2022]
- Dr. Deepak Chopra Aligns with Plant-Based Therapeutics Company ProVEDA to Highlight Topical Pain Relief Solutions - Yahoo Finance - October 19th, 2022 [October 19th, 2022]
- True REST Float Spa Offers Free Floatation Therapy Session to Veterans - AccessWire - October 19th, 2022 [October 19th, 2022]
- Youve been told you need surgery for degenerative disc disease and stenosis of the spine. Now what? - Sonoran News - October 19th, 2022 [October 19th, 2022]
- Can you take Paxlovid and heart disease medications at the same time? - Medical News Today - October 15th, 2022 [October 15th, 2022]
- Kardashian fans think theyve unlocked Kourtneys secret to hiding her pregnancy after spotting key detai... - The US Sun - October 15th, 2022 [October 15th, 2022]
- Cabinet approves B5bn for 'Andaman International Health Center' - The Phuket News - October 15th, 2022 [October 15th, 2022]
- Eye health and dynamics of the modern world - The Citizen - October 15th, 2022 [October 15th, 2022]
- The Holistic Review on Occurrence, Biology, Diagnosis, and Treatment of Oral Squamous Cell Carcinoma - Cureus - October 15th, 2022 [October 15th, 2022]
- 10 Deeper Causes of Tinnitus, and How to Treat It - The Epoch Times - October 15th, 2022 [October 15th, 2022]
- Complementary and Alternative Medicine (CAM) - GoodTherapy - October 13th, 2022 [October 13th, 2022]
- India's alternative medicine industry grows, boosted by COVID-19 pandemic - CNA - October 13th, 2022 [October 13th, 2022]
- QC Kinetix (Charlotte) Offers Alternative Treatments for Knee Pain and Sports Injuries - Yahoo Finance - October 13th, 2022 [October 13th, 2022]
- Plant Extracts Market is expected to generate a revenue of USD 85.09 Billion by 2030, Globally, at 6.33% CAGR: Verified Market Research - Yahoo... - October 13th, 2022 [October 13th, 2022]
- Neuroplasticity Nonsense Is Full of Red Flags - Science Based Medicine - October 13th, 2022 [October 13th, 2022]
- Diabetics won't be made to pay for alternative medicines, Pharmac says - Stuff - October 13th, 2022 [October 13th, 2022]
- Lili Reinhart Becomes A Reiki Master: My Journey Into Reiki Healing Cant Be Simplified - IMDb - October 13th, 2022 [October 13th, 2022]
- The DRIPBaR is Coming to Clarksville, TN on Oct 16, 2022 - PR Web - October 13th, 2022 [October 13th, 2022]
- How Dr. Oz Boosted an Osteopath Who Became a Top Spreader of Covid Misinformation Mother Jones - Mother Jones - October 13th, 2022 [October 13th, 2022]
- World Arthritis Day: Arthritis and Women - Times of India - October 13th, 2022 [October 13th, 2022]
- What Is Alternative Medicine? - American Cancer Society - October 6th, 2022 [October 6th, 2022]
- Herbal medicine: Types, uses, and safety - Medical News Today - October 6th, 2022 [October 6th, 2022]
- WCI Health LLC, Your Alternative Health and Wellness Hub Will Be a Vendor and Presenter at Wonderland Miami by Microdose - StreetInsider.com - October 6th, 2022 [October 6th, 2022]
- The Viral Real - Journal #130 October 2022 - E-Flux - October 6th, 2022 [October 6th, 2022]
- Pregabalin Market to Grow by USD 153.03 Mn from 2022 to 2026, Driven by Presence of Large Patient Pool Related To Neuropathic Pain - Technavio - Yahoo... - October 6th, 2022 [October 6th, 2022]
- Woman, 37, dies after herbal supplements led to liver failure: coroner - Insider - October 6th, 2022 [October 6th, 2022]
- What Is Vitiligo? All About This Unique Skin Condition That Impacts Skin Pigmentation, and How To Treat It - Parade Magazine - October 6th, 2022 [October 6th, 2022]
- Herbalist's Resource Guide to Cannabis and Other Plants That Can Prevent Cancer - PR Web - October 6th, 2022 [October 6th, 2022]
- Tasly Pharmaceuticals to Exhibit at BioJapan 2022 -- Bio-Pharmaceutical Company to Join with Maryland-Bas - Benzinga - October 6th, 2022 [October 6th, 2022]
- "Sh*t, I just want to get better. Thats what pushed me to do it, and it worked well" Chauncey Billups and other NBA stars on acupuncture -... - October 6th, 2022 [October 6th, 2022]
- People Science and Symbiome Partner to study the microbiome in the real world - Benzinga - October 6th, 2022 [October 6th, 2022]
- Bob Newhart Proves 93 Is the New 39 - Eat This, Not That - September 29th, 2022 [September 29th, 2022]
- Medical cannabis could be better alternative to opioids in managing pain - The Tribune India - September 29th, 2022 [September 29th, 2022]
- Woman killed by herbal remedies she took to treat arthritis - Evening Standard - September 29th, 2022 [September 29th, 2022]
- Get To Know The Best Natural Adderall Alternatives - Over The Counter and Non Prescription - Outlook India - September 29th, 2022 [September 29th, 2022]
- King Charles III Has a History of Promoting 'Quackery' Alternative Medicine - Newsweek - September 9th, 2022 [September 9th, 2022]
- Remedy Place: The Fashionable Social Wellness Club Where You Can Bring All Your Friends - Vogue - September 9th, 2022 [September 9th, 2022]
- Thailand heightens its healthcare hub ambition with integrative medicine - PR Newswire UK - September 9th, 2022 [September 9th, 2022]
- How bogus cancer treatments prey on the most vulnerable - Coda Story - September 9th, 2022 [September 9th, 2022]
- Management of Chronic Migraine in Children and Adolescents | PHMT - Dove Medical Press - September 9th, 2022 [September 9th, 2022]
- Mouth Taping: Is It Safe? - Health Essentials - September 9th, 2022 [September 9th, 2022]
- Queen Elizabeth: Seven things you need to know about the Queens passing - Toronto Star - September 9th, 2022 [September 9th, 2022]
- Building an Alternative Medical Economy in Response to 'Tyranny': Telehealth CEO - The Epoch Times - August 30th, 2022 [August 30th, 2022]
- Sesame oil: Nutrition, benefits, and more - Medical News Today - August 30th, 2022 [August 30th, 2022]
- Regenerative Medicine: An alternative to surgery and pills | Loop Cayman Islands - Loop News Cayman - August 30th, 2022 [August 30th, 2022]
- Find Euphoria: the luxury Greek spa retreat to visit now - Tatler - August 30th, 2022 [August 30th, 2022]
- What Is Synthetic Urine & How Does It Help To Pass A Drug Test? - The Island Now - August 30th, 2022 [August 30th, 2022]
- The science behind the healthtech startup must be understood well - Express Healthcare - August 30th, 2022 [August 30th, 2022]
- Best-in-class second-line HIV treatment rolls out in Zambia and Nigeria - Clinton Health Access Initiative - August 30th, 2022 [August 30th, 2022]
- Therapeutic effect of HFNC and NIV in patients with AECOPD | COPD - Dove Medical Press - August 30th, 2022 [August 30th, 2022]
- Five years after Kymriah: Ensuring the next cell and gene therapies reach patients - STAT - August 30th, 2022 [August 30th, 2022]
- Meet these renowned healthcare professionals who assist us in leading healthier lives - Oneindia - August 30th, 2022 [August 30th, 2022]
- Diet and Vitiligo: The Story So Far - Cureus - August 29th, 2022 [August 29th, 2022]
- Fatphobia Sucks, Especially If You're Trying to Have a Baby - VICE - August 29th, 2022 [August 29th, 2022]
- Orthomolecular Medicine, A Predictive Tool - Nation World News - August 29th, 2022 [August 29th, 2022]
- COVID-19 vaccines and the Nuremberg Code - Science Based Medicine - August 29th, 2022 [August 29th, 2022]
- Bolstering the Blood-CNS Barrier Could Lead to New Treatment Approach for Multiple Sclerosis - University of Utah Health Care - August 29th, 2022 [August 29th, 2022]
- Lockdowns Postponed the Inevitable. Is That a Bad Thing? - Science Based Medicine - August 29th, 2022 [August 29th, 2022]
- The Impact of Complementary and Alternative Medicine on Insomnia: A Systematic Review - Cureus - August 27th, 2022 [August 27th, 2022]
- Ayurveda As Alternative Medicine: Research And Development To Be Taken Ahead By Heal In India - Entrepreneur - August 27th, 2022 [August 27th, 2022]
- French Doctolib platform accused of 'promoting alternative medicine' - The Connexion - August 27th, 2022 [August 27th, 2022]
- Chronic Fatigue Syndrome: Best Ways for Treating This Condition - Healthline - August 27th, 2022 [August 27th, 2022]
- Ellen White reveals "traumatic" incident that played huge role in her retirement - GIVEMESPORT - August 27th, 2022 [August 27th, 2022]
- Curcumin and Non-Hodgkin's Lymphoma: Does It Help? - Healthline - August 27th, 2022 [August 27th, 2022]
- In Denial: When Patients Don't Want to Believe They Have Cancer - Medscape - August 27th, 2022 [August 27th, 2022]
- Piotr Szyhalski depicts living through COVID-19 and other extreme historical phenomena - MinnPost - August 27th, 2022 [August 27th, 2022]
- Researchers identify chemo alternative for targeted treatment of leukemia patients - Devdiscourse - August 27th, 2022 [August 27th, 2022]
- India Can Show The World The Right Path For Medical Pluralism - News18 - August 27th, 2022 [August 27th, 2022]
- Complementary and Integrative Medicine - Reeve Foundation - Christopher Reeve Foundation - August 23rd, 2022 [August 23rd, 2022]
- Back pain: Exploring alternative treatments - Health - Life & Style - Ahram Online - August 23rd, 2022 [August 23rd, 2022]