Epigallocatechin Gallate from Green Tea Effectively Blocks Infection of SARS-CoV-2 and New Variants by Inhibiting Spike Binding to ACE2 Receptor

Liu, Jinbiao; Bodnar, Brittany; Meng, Feng-Zhen; Khan, Adil I.; Wang, Xu; Luo, Guangxiang; Saribas, Sami; Wang, Tao; Lohani, Saroj Chandra; Wang, Peng; Wei, Zhengyu; Luo, Jin Jun; Zhou, Lina; Wu, Jianhui; Li, Qingsheng; Hu, Wenhui; Ho, Wen‐Zhe

doi:10.1101/2021.03.17.435637

Cited by 5 publications

(9 citation statements)

References 60 publications

(42 reference statements)

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“…The fact that EGCG is more potent at preventing SARS-CoV-2 entry than replication agrees with the previous reports of lentiviral assays [ 2 ]. A growing body of data suggests that the preventive activity is due to EGCG interference with the interactions between SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) [ 2 , 7 , 8 ]. This is attributable to EGCG binding with spike (S) protein [ 10 ].…”

Section: Resultssupporting

confidence: 92%

“…The two subunits of the entry-mediating virus surface spike protein (S1, which recognizes ACE2 receptor via its receptor binding domain, and S2, which mediates membrane fusion) have been considered previously as EGCG binding partners. Indirect assays argued against the decisive role of S2; while recombinant S1 showed affinity for EGCG in the micromolar concentration range [ 2 ]. Consistently with the data in the literature, we observed only weak EGCG binding with the fluorescently labeled S2 in microscale thermophoresis (MST)-based in vitro assays: Kd = 54 ± 6 μМ ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1 A), a major component of the green tea extract, is currently in the limelight, as it shows pronounced inhibitory activity against various types of viruses, especially with positive-sense single-stranded RNA genomes [ 1 ]. Discussions on EGCG applicability for SARS-CoV-2 treatment or prevention are mostly grounded by the results of lentiviral system-based assays [ 2 ]. Direct evidence for EGCG activity against SARS-CoV-2 is limited [ 3 ], and detailed experiments with the live virus and various treatment schemes are much needed.…”

Section: Introductionmentioning

confidence: 99%

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EGCG as an anti-SARS-CoV-2 agent: Preventive versus therapeutic potential against original and mutant virus

et al. 2021

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In the search for anti-SARS-CoV-2 drugs, much attention is given to safe and widely available native compounds. The green tea component epigallocatechin 3 gallate (EGCG) is particularly promising because it reportedly inhibits viral replication and viral entry in vitro . However, conclusive evidence for its predominant activity is needed. We tested EGCG effects on the native virus isolated from COVID-19 patients in two independent series of experiments using VERO cells and two different treatment schemes in each series. The results confirmed modest cytotoxicity of EGCG and its substantial antiviral activity. The preincubation scheme aimed at infection prevention has proven particularly beneficial. We complemented that finding with a detailed investigation of EGCG interactions with viral S-protein subunits, including S2, RBD, and the RBD mutant harboring the N501Y mutation. Molecular modeling experiments revealed N501Y-specific stacking interactions in the RBD-ACE2 complex and provided insight into EGCG interference with the complex formation. Together, these findings provide a molecular basis for the observed EGCG effects and reinforce its prospects in COVID-19 prevention therapy.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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EGCG as an anti-SARS-CoV-2 agent: Preventive versus therapeutic potential against original and mutant virus

et al. 2021

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“…EGCG had better docking scores among the others, although the difference was not significant. This is in agreement with previous reports [ 31 , 43 ]. The same trend is followed for wild and mutated strains.…”

Section: Resultssupporting

confidence: 94%

Entry-inhibitory role of catechins against SARS-CoV-2 and its UK variant

Mhatre

Gurav

Shah

et al. 2021

Computers in Biology and Medicine

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Background The global pandemic caused by an RNA virus capable of infecting humans and animals, has resulted in millions of deaths worldwide. Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infects the lungs and the gastrointestinal tract to some extent. Rapid structural mutations have increased the virulence and infectivity of the virus drastically. One such mutated strain known as the UK variant has caused many deaths in the United Kingdom. Hypothesis Among several indigenous natural ingredients used for prevention and cure of many diseases, the catechins have been reported for their antiviral activity, even against SARS-CoV-2. Characteristic mutations present on the spike protein have presented the newer strain its enhanced infectivity. The spike protein helps the virus bind to ACE2 receptor of the host cell and hence is a drug target. Catechins have been reported for their entry-inhibitory activity against several viruses. Method In this study, we performed molecular docking of different catechins with the wild and mutant variants of the spike protein of SARS-CoV-2. The stability of the best docked complexes was validated using molecular dynamics simulation. Results The in-silico studies show that the catechins form favourable interactions with the spike protein and can potentially impair its function. Epigallocatechin gallate (EGCG) showed the best binding among the catechins against both the strains. Both the protein-ligand complexes were stable throughout the simulation time frame. Conclusion The outcomes should encourage further exploration of the antiviral activity of EGCG against SARS-CoV-2 and its variants.

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“…These compounds are even effective against Zika, Chikungunya, and Dengue viruses (23). Recent computational and experimental investigations documented the potent antiviral activities of bioactive tea molecules against multiple vital proteins, including the main protease (Mpro), non-structural protein 15 (Nsp15), spike, and RdRp of SARS-CoV-2 (24)(25)(26)(27)(28). The main objectives of the study were to analyze the interaction pattern and binding affinity of selected bioactive molecules and FDA-approved antiviral drugs with the active pocket of SARS-CoV-2 RdRp and, furthermore, to rank and suggest topmost molecules on the basis of their potential to hinder the replication process of SARS-CoV-2.…”

Section: Graphical Abstract |mentioning

confidence: 99%

Bioactive Molecules of Tea as Potential Inhibitors for RNA-Dependent RNA Polymerase of SARS-CoV-2

et al. 2021

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The coronavirus disease (COVID-19), a worldwide pandemic, is caused by the severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2). At this moment in time, there are no specific therapeutics available to combat COVID-19. Drug repurposing and identification of naturally available bioactive molecules to target SARS-CoV-2 are among the key strategies to tackle the notorious virus. The enzyme RNA-dependent RNA polymerase (RdRp) performs a pivotal role in replicating the virus. RdRp is a prime target for Remdesivir and other nucleotides analog-based antiviral drugs. In this study, we showed three bioactive molecules from tea (epicatechin-3,5-di-O-gallate, epigallocatechin-3,5-di-O-gallate, and epigallocatechin-3,4-di-O-gallate) that showed better interaction with critical residues present at the catalytic center and the NTP entry channel of RdRp than antiviral drugs Remdesivir and Favipiravir. Our computational approach to identify these molecules included molecular docking studies, followed by robust molecular dynamics simulations. All the three molecules are readily available in tea and could be made accessible along with other medications to treat COVID-19 patients. However, these results require validation by further in vitro and in vivo studies.

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Epigallocatechin Gallate from Green Tea Effectively Blocks Infection of SARS-CoV-2 and New Variants by Inhibiting Spike Binding to ACE2 Receptor

Cited by 5 publications

References 60 publications

EGCG as an anti-SARS-CoV-2 agent: Preventive versus therapeutic potential against original and mutant virus

EGCG as an anti-SARS-CoV-2 agent: Preventive versus therapeutic potential against original and mutant virus

Entry-inhibitory role of catechins against SARS-CoV-2 and its UK variant

Bioactive Molecules of Tea as Potential Inhibitors for RNA-Dependent RNA Polymerase of SARS-CoV-2

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