An Overview on the Potential Roles of EGCG in the Treatment of COVID-19 Infection

Figures & data

Table 1 A Summary of Pre-Clinical Studies on the Antiviral Activity of EGCG Against SARS-Cov-2

Substance	Effect	Reference
EGCG, TF3, TFs	TF3 and EGCG by interacting with the receptors present in SARS-CoV-2 virus, thus inhibiting its replication. TFs bind to Spike RBD.	[^Citation58]
EGCG, GTE	EGCG and GTE are able to control the inflammation damage occurring in SARS-CoV-2 infection by acting on STAT, NF-κB, Nrf2 signaling pathways.	[^Citation59]
EGCG, TQ, VITAMIN D3	The combination of EGCG, TQ AND VITAMIN D3 activates Nrf2-dependent genes thus preventing the cells against SARS-CoV-2 infection.	[^Citation60]
EGCG, TF1, TF2a, TF2b, hesperidin, quercetagetin, and myricetin	EGCG, TF1, TF2a, TF2b, TF3 bind stably to the active site of RdRp.	[^Citation61]
SA, L-PGA, N-NPTA, ACPS, EGCG, KDH and SeM	ACPS and KDH are powerful species in the treatment of SARS-CoV-2 infection.	[^Citation62]
EGCG and TFs in HEK2937	EGCG and TF inhibited activity against the SARS-CoV-2 3CL-protease, in dose dependent manner e without citotoxity for treated cells.	[^Citation63]
EGCG, withaferin A, dolutegravir and artesunate	EGCG, withaferin A, dolutegravir and artesunate could be considered potential drugs for SARS-CoV-2 infection.	[^Citation64]
EGCG and TF3	EGCG and TF3 possess broad-spectrum antiviral activity in treatment of SARS-CoV-2 infection.	[^Citation65]
Flavan-3-ols and PAs	CAG, ECG, GCG, and EGCG inhibited the M^pro activity of SARS-CoV-2.	[^Citation66]
Trans-resveratrol, EGCG and BX795	Trans-resveratrol, EGCG and BX795 show multiple antiviral effects against SARS-CoV-2.	[^Citation67]
PGG, EGCG	PGG, EGCG inhibited the viral protease activity of SARS-CoV-2 3CLpro	[^Citation68]
EGCG, active ingredients of TCM	EGCG inhibits the 3CLpro activity of SARS-CoV-2.	[^Citation69]
EGCG	EGCG inhibits HCoV-OC43 and HCoV-229E replication.	[^Citation70]
EGCG, EGC	EGCG and EGC inhibited PLPro	[^Citation71]
EGCG	EGCG arrested the entry of SARS-CoV-2, MERS and SARS-CoV pseudotyped lentiviral vectors and restrained virus infections. An inhibition of the SARS-CoV-2 spike–receptor interaction was also detected.	[^Citation72]

Abbreviations: EGCG, epigallocatechin-3-gallate; TF3, theaflavin-3,3′-digallate; TFs, theaflavins; RBD, receptor-binding domain; STAT, signal transducer and activator of transcription; NF-κb, nuclear factor kappa-light-chain-enhancer of activated B cells; Nrf2, nuclear factor erythroid-derived 2-related factor 2; TQ, thymoquinone; RdRp, RNA-dependent RNA polymerase; SA, succinic acid; L-PGA, L-pyroglutamic acid; N-NPTA, N-phenyl-thioacetamide; ACPS, 2-amino-5-chloropyridine hydrogen succinate; KDH, 2-oxoglutarate dehydrogenase E1 component, putative; SeM, selenomethionine; PAs, proanthocyanidins; M^pro, main protease; CAG, catechin-3-O-gallate; ECG, (–)-epicatechin-3-O-gallate; PA2, procyanidin A2; PB2, procyanidin B2; PGG, 1,2,3,4,6-pentagalloylglucose; 3CLpro, chymotrypsin-like protease; TCM, traditional medicine; HCoV-OC43, beta coronavirus; HCoV-229E, alpha coronavirus; PLPro, papain-like protease protein.

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 α; pp1ab, 2ʹ-O-methyltransferase; Mpro, main protease; ACE2, angiotensin-converting enzyme 2; S-protein, spike protein; RdRp, RNA-dependent RNA polymerase.

MhatreS, SrivastavaT, NaikS, PatravaleV. 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.2020.15328632741697

 PubMed Web of Science ®Google Scholar

MenegazziM, CampagnariR, BertoldiM, CrupiR, Di PaolaR, CuzzocreaS. 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

 PubMed Web of Science ®Google Scholar

MendoncaP, SolimanKFA. 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

 Web of Science ®Google Scholar

SinghS, SkMF, SonawaneA, KarP, SadhukhanS. 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;28:1–16. doi:10.1080/07391102.2020.1796810

 Web of Science ®Google Scholar

SagaamaA, BrandanSA, Ben IssaT, IssaouiN. 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.e0464032802981

 PubMed Web of Science ®Google Scholar

JangM, ParkYI, ChaYE, 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:10.1155/2020/563083832963564

 PubMed Web of Science ®Google Scholar

SharmaS, DeepS. In-silico drug repurposing for targeting SARS-CoV-2 main protease (Mpro). J Biomol Struct Dyn. 2020;12:1–8. doi:10.1080/07391102.2020.1844058

 Web of Science ®Google Scholar

MhatreS, NaikS, PatravaleV. 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.2020.10413733302163

 PubMed Web of Science ®Google Scholar

ZhuY, XieDY. 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.2020.60131633329667

 PubMed Web of Science ®Google Scholar

WangT, ZhaoM, YeP, WangQ, ZhaoY. Integrated bioinformatics analysis for the screening of associated pathways and therapeutic drugs in coronavirus disease 2019. Arch Med Res. 2021;52(3):304–310. doi:10.1016/j.arcmed.2020.11.00933309308

 PubMed Web of Science ®Google Scholar

ChiouWC, ChenJC, ChenYT, 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

 Web of Science ®Google Scholar

DuA, ZhengR, DisomaC, 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;176:1–12. doi:10.1016/j.ijbiomac.2021.02.01233548314

 PubMed Web of Science ®Google Scholar

JangM, ParkR, ParkYI, et al. EGCG, a green tea polyphenol, inhibits human coronavirus replication in vitro. Biochem Biophys Res Commun. 2021;547:23–28. doi:10.1016/j.bbrc.2021.02.01633588235

 PubMed Web of Science ®Google Scholar

ChourasiaM, KoppulaPR, BattuA, OusephMM, SinghAK. 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/molecules2605120033668085

 PubMed Web of Science ®Google Scholar

HenssL, AusteA, SchürmannC, 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

 PubMed Web of Science ®Google Scholar