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Interaction of Epigallocatechin Gallate and Quercetin with Spike Glycoprotein (S-Glycoprotein) of SARS-CoV-2: In Silico Study

Alavi et al., Biomedicines, doi:10.3390/biomedicines10123074

Nov 2022

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Quercetin for COVID-19

22nd treatment shown to reduce risk in July 2021

^*, now known with p = 0.0031 from 11 studies.

Lower risk for ICU admission, hospitalization, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,100+ studies for 60+ treatments. c19early.org

In Silico study suggesting efficacy of epigallocatechin gallate and quercetin for SARS-CoV-2.

53 preclinical studies support the efficacy of quercetin for COVID-19:

32 In Silico studies Ahmed, Akinwumi, Alanzi, Alavi, Alkafaas, Azmi, Chandran, Chellasamy, Corbo, El-Megharbel, Hasanah, Ibeh, Kandeil, Mandal, Moschovou, Nguyen, Pan, Qin, Rehman, Sai Ramesh, Sekiou, Shaik, Singh, Singh (B), Thapa, Wang, Waqas, Yang, Yang (B), Zhang, Zhou, Şimşek

16 In Vitro studies Aguado, Bahun, DiGuilio, El-Megharbel, Fang, Goc, Kandeil, Munafò, Pan, Roy, Singh (C), Waqas, Wu, Xu, Yang, Zhang (B)

5 In Vivo animal studies Aguado, El-Megharbel, Shaker, Wu, Wu (B)

In Silico studies predict inhibition of SARS-CoV-2, or minimization of side effects, with quercetin or metabolites via binding to the spike Note A, Alavi, Azmi (B), Chandran, Kandeil, Mandal, Moschovou, Nguyen, Pan, Thapa (B), Şimşek, M^pro Note B, Akinwumi, Alanzi, Ibeh, Kandeil, Mandal, Moschovou, Nguyen, Qin, Rehman, Sekiou (B), Singh, Thapa (B), Wang, Zhang, Shaik, Waqas, RNA-dependent RNA polymerase Note C, Corbo, PLpro Note D, Ibeh, Zhang, ACE2 Note E, Chandran, Ibeh, Qin, Thapa (B), Şimşek, Alkafaas, TMPRSS2 Note F, Chandran, helicase Note G, Alanzi, Singh (B), endoribonuclease Note H, Alavi, cathepsin L Note I, Ahmed, Wnt-3 Note J, Chandran, FZD Note K, Chandran, LRP6 Note L, Chandran, ezrin Note M, Chellasamy, ADRP Note N, Nguyen, NRP1 Note O, Şimşek, EP300 Note P, Hasanah, PTGS2 Note Q, Qin, HSP90AA1 Note R, Qin, Hasanah, matrix metalloproteinase 9 Note S, Sai Ramesh, IL-6 Note T, Yang, Yang (B), IL-10 Note U, Yang, VEGFA Note V, Yang (B), and RELA Note W, Yang (B) proteins. In Vitro studies demonstrate efficacy in Calu-3 Note X, DiGuilio, A549 Note Y, Yang, HEK293-ACE2+ Note Z, Singh (C), Huh-7 Note AA, Pan, Caco-2 Note AB, Roy, Vero E6 Note AC, Kandeil, El-Megharbel, Roy, mTEC Note AD, Wu, and RAW264.7 Note AE, Wu cells. Animal studies demonstrate efficacy in K18-hACE2 mice Note AF, Aguado, db/db mice Note AG, Wu, Wu (B), BALB/c mice Note AH, Shaker, and rats El-Megharbel (B). Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice Shaker.

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1. Aguado et al., Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology, bioRxiv, doi:10.1101/2023.01.17.524329.biorxiv.org, doi.org.

2. Ahmed et al., Evaluation of the Effect of Zinc, Quercetin, Bromelain and Vitamin C on COVID-19 Patients, International Journal of Diabetes Management, doi:10.61797/ijdm.v2i2.259.researchlakejournals.com, doi.org.

3. Akinwumi et al., Evaluation of therapeutic potentials of some bioactive compounds in selected African plants targeting main protease (Mpro) in SARS-CoV-2: a molecular docking study, Egyptian Journal of Medical Human Genetics, doi:10.1186/s43042-023-00456-4.springeropen.com, doi.org.

4. Alanzi et al., Structure-based virtual identification of natural inhibitors of SARS-CoV-2 and its Delta and Omicron variant proteins, Future Virology, doi:10.2217/fvl-2022-0184.futuremedicine.com, doi.org.

5. Alavi et al., Interaction of Epigallocatechin Gallate and Quercetin with Spike Glycoprotein (S-Glycoprotein) of SARS-CoV-2: In Silico Study, Biomedicines, doi:10.3390/biomedicines10123074.mdpi.com, doi.org.

6. Alkafaas et al., A study on the effect of natural products against the transmission of B.1.1.529 Omicron, Virology Journal, doi:10.1186/s12985-023-02160-6.biomedcentral.com, doi.org.

7. Azmi et al., Utilization of quercetin flavonoid compounds in onion (Allium cepa L.) as an inhibitor of SARS-CoV-2 spike protein against ACE2 receptors, 11th International Seminar on New Paradigm and Innovation on Natural Sciences and its Application, doi:10.1063/5.0140285.scitation.org, doi.org.

8. Azmi (B) et al., The role of vitamin D receptor and IL‐6 in COVID‐19, Molecular Genetics & Genomic Medicine, doi:10.1002/mgg3.2172.wiley.com, doi.org.

9. Bahun et al., Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols, Food Chemistry, doi:10.1016/j.foodchem.2021.131594.sciencedirect.com, doi.org.

10. Chandran et al., Molecular docking analysis of quercetin with known CoVid-19 targets, Bioinformation, doi:10.6026/973206300191081.bioinformation.net, doi.org.

11. Chellasamy et al., Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors, Journal of King Saud University - Science, doi:10.1016/j.jksus.2022.102277.sciencedirect.com, doi.org.

12. Corbo et al., Inhibitory potential of phytochemicals on five SARS-CoV-2 proteins: in silico evaluation of endemic plants of Bosnia and Herzegovina, Biotechnology & Biotechnological Equipment, doi:10.1080/13102818.2023.2222196.tandfonline.com, doi.org.

13. DiGuilio et al., Quercetin improves and protects Calu-3 airway epithelial barrier function, Frontiers in Cell and Developmental Biology, doi:10.3389/fcell.2023.1271201.frontiersin.org, doi.org.

14. El-Megharbel et al., Chemical and spectroscopic characterization of (Artemisinin/Quercetin/ Zinc) novel mixed ligand complex with assessment of its potent high antiviral activity against SARS-CoV-2 and antioxidant capacity against toxicity induced by acrylamide in male rats, PeerJ, doi:10.7717/peerj.15638.peerj.com, doi.org.

15. El-Megharbel (B) et al., Chemical and spectroscopic characterization of (Artemisinin/Quercetin/ Zinc) novel mixed ligand complex with assessment of its potent high antiviral activity against SARS-CoV-2 and antioxidant capacity against toxicity induced by acrylamide in male rats, PeerJ, doi:10.7717/peerj.15638.peerj.com, doi.org.

16. Fang et al., Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19, Journal of Nanobiotechnology, doi:10.1186/s12951-024-02435-2.biomedcentral.com, doi.org.

17. Goc et al., Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants, European Journal of Microbiology and Immunology, doi:10.1556/1886.2021.00022.akjournals.com, doi.org.

18. Hasanah et al., Decoding the therapeutic potential of empon-empon: a bioinformatics expedition unraveling mechanisms against COVID-19 and atherosclerosis, International Journal of Applied Pharmaceutics, doi:10.22159/ijap.2024v16i2.50128.innovareacademics.in, doi.org.

19. Ibeh et al., Computational studies of potential antiviral compounds from some selected Nigerian medicinal plants against SARS-CoV-2 proteins, Informatics in Medicine Unlocked, doi:10.1016/j.imu.2023.101230.sciencedirect.com, doi.org.

20. Kandeil et al., Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2, Pathogens, doi:10.3390/pathogens10060758.mdpi.com, doi.org.

21. Mandal et al., In silico anti-viral assessment of phytoconstituents in a traditional (Siddha Medicine) polyherbal formulation – Targeting Mpro and pan-coronavirus post-fusion Spike protein, Journal of Traditional and Complementary Medicine, doi:10.1016/j.jtcme.2023.07.004.sciencedirect.com, doi.org.

22. Moschovou et al., Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein, International Journal of Molecular Sciences, doi:10.3390/ijms242115894.mdpi.com, doi.org.

23. Munafò et al., Quercetin and Luteolin Are Single-digit Micromolar Inhibitors of the SARS-CoV-2 RNA-dependent RNA Polymerase, Research Square, doi:10.21203/rs.3.rs-1149846/v1.researchsquare.com, doi.org.

24. Nguyen et al., The Potential of Ameliorating COVID-19 and Sequelae From Andrographis paniculata via Bioinformatics, Bioinformatics and Biology Insights, doi:10.1177/11779322221149622.sagepub.com, doi.org.

25. Pan et al., Quercetin: A promising drug candidate against the potential SARS-CoV-2-Spike mutants with high viral infectivity, Computational and Structural Biotechnology Journal, doi:10.1016/j.csbj.2023.10.029.sciencedirect.com, doi.org.

26. Qin et al., Exploring the bioactive compounds of Feiduqing formula for the prevention and management of COVID-19 through network pharmacology and molecular docking, Medical Data Mining, doi:10.53388/MDM202407003.tmrjournals.com, doi.org.

27. Rehman et al., Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and Simulation Approach to Combat COVID-19, Current Pharmaceutical Design, doi:10.2174/1381612826999201116195851.doi.org, doi.org.

28. Roy et al., Quercetin inhibits SARS-CoV-2 infection and prevents syncytium formation by cells co-expressing the viral spike protein and human ACE2, Virology Journal, doi:10.1186/s12985-024-02299-w.biomedcentral.com, doi.org.

29. Sai Ramesh et al., Computational analysis of the phytocompounds of Mimusops elengi against spike protein of SARS CoV2 – An Insilico model, International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2023.125553.sciencedirect.com, doi.org.

30. Sekiou et al., In-Silico Identification of Potent Inhibitors of COVID-19 Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from Natural Products: Quercetin, Hispidulin, and Cirsimaritin Exhibited Better Potential Inhibition than Hydroxy-Chloroquine Against COVID-19 Main Protease Active Site and ACE2, ChemRxiv, doi:10.26434/chemrxiv.12181404.v1.chemrxiv.org, doi.org.

31. Sekiou (B) et al., In-Silico Identification of Potent Inhibitors of COVID-19 Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from Natural Products: Quercetin, Hispidulin, and Cirsimaritin Exhibited Better Potential Inhibition than Hydroxy-Chloroquine Against COVID-19 Main Protease Active Site and ACE2, ChemRxiv, doi:10.26434/chemrxiv.12181404.v1.chemrxiv.org, doi.org.

32. Shaik et al., Computational identification of selected bioactive compounds from Cedrus deodara as inhibitors against SARS-CoV-2 main protease: a pharmacoinformatics study, Indian Drugs, doi:10.53879/id.61.02.13859.indiandrugsonline.org, doi.org.

33. Shaker et al., Anti-cytokine Storm Activity of Fraxin, Quercetin, and their Combination on Lipopolysaccharide-Induced Cytokine Storm in Mice: Implications in COVID-19, Iranian Journal of Medical Sciences, doi:10.30476/ijms.2023.98947.3102.ac.ir, doi.org.

34. Şimşek et al., In silico identification of SARS-CoV-2 cell entry inhibitors from selected natural antivirals, Journal of Molecular Graphics and Modelling, doi:10.1016/j.jmgm.2021.108038.sciencedirect.com, doi.org.

35. Singh et al., Unlocking the potential of phytochemicals in inhibiting SARS-CoV-2 M Pro protein - An in-silico and cell-based approach, Research Square, doi:10.21203/rs.3.rs-3888947/v1.researchsquare.com, doi.org.

36. Singh (B) et al., Flavonoids as Potent Inhibitor of SARS-CoV-2 Nsp13 Helicase: Grid Based Docking Approach, Middle East Research Journal of Pharmaceutical Sciences, doi:10.36348/merjps.2023.v03i04.001.kspublisher.com, doi.org.

37. Singh (C) et al., The spike protein of SARS-CoV-2 virus induces heme oxygenase-1: Pathophysiologic implications, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, doi:10.1016/j.bbadis.2021.166322.sciencedirect.com, doi.org.

38. Thapa et al., In-silico Approach for Predicting the Inhibitory Effect of Home Remedies on Severe Acute Respiratory Syndrome Coronavirus-2, Makara Journal of Science, doi:10.7454/mss.v27i3.1609.ac.id, doi.org.

39. Thapa (B) et al., In-silico Approach for Predicting the Inhibitory Effect of Home Remedies on Severe Acute Respiratory Syndrome Coronavirus-2, Makara Journal of Science, doi:10.7454/mss.v27i3.1609.ac.id, doi.org.

40. Wang et al., Computational Analysis of Lianhua Qingwen as an Adjuvant Treatment in Patients with COVID-19, Society of Toxicology Conference, 2023, www.researchgate.net/publication/370491709_Y_Wang_A_E_Tan_O_Chew_A_Hsueh_and_D_E_Johnson_2023_Computational_Analysis_of_Lianhua_Qingwen_as_an_Adjuvant_Treatment_in_Patients_with_COVID-19_Toxicologist_1921_507.researchgate.net.

41. Waqas et al., Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics, Current Medicinal Chemistry, doi:10.2174/0109298673292839240329081008.eurekaselect.com, doi.org.

42. Wu et al., SARS-CoV-2 N protein induced acute kidney injury in diabetic db/db mice is associated with a Mincle-dependent M1 macrophage activation, Frontiers in Immunology, doi:10.3389/fimmu.2023.1264447.frontiersin.org, doi.org.

43. Wu (B) et al., Treatment with Quercetin inhibits SARS-CoV-2 N protein-induced acute kidney injury by blocking Smad3-dependent G1 cell cycle arrest, Molecular Therapy, doi:10.1016/j.ymthe.2022.12.002.sciencedirect.com, doi.org.

44. Xu et al., Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19, Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2301775120.pnas.org, doi.org.

45. Yang et al., Active ingredient and mechanistic analysis of traditional Chinese medicine formulas for the prevention and treatment of COVID-19: Insights from bioinformatics and in vitro experiments, Medicine, doi:10.1097/MD.0000000000036238.lww.com, doi.org.

46. Yang (B) et al., In silico evidence implicating novel mechanisms of Prunella vulgaris L. as a potential botanical drug against COVID-19-associated acute kidney injury, Frontiers in Pharmacology, doi:10.3389/fphar.2023.1188086.frontiersin.org, doi.org.

47. Zhang et al., In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus, Journal of Integrative Medicine, doi:10.1016/j.joim.2020.02.005.sciencedirect.com, doi.org.

48. Zhang (B) et al., Discovery of the covalent SARS‐CoV‐2 M^pro inhibitors from antiviral herbs via integrating target‐based high‐throughput screening and chemoproteomic approaches, Journal of Medical Virology, doi:10.1002/jmv.29208.wiley.com, doi.org.

49. Zhou et al., Bioinformatics and system biology approaches to determine the connection of SARS-CoV-2 infection and intrahepatic cholangiocarcinoma, PLOS ONE, doi:10.1371/journal.pone.0300441.plos.org, doi.org.

a. The trimeric spike (S) protein is a glycoprotein that mediates viral entry by binding to the host ACE2 receptor, is critical for SARS-CoV-2's ability to infect host cells, and is a target of neutralizing antibodies. Inhibition of the spike protein prevents viral attachment, halting infection at the earliest stage.

b. The main protease or M^pro, also known as 3CL^pro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting M^pro disrupts the SARS-CoV-2 lifecycle within the host cell, preventing the creation of new copies.

c. RNA-dependent RNA polymerase (RdRp), also called nsp12, is the core enzyme of the viral replicase-transcriptase complex that copies the positive-sense viral RNA genome into negative-sense templates for progeny RNA synthesis. Inhibiting RdRp blocks viral genome replication and transcription.

d. The papain-like protease (PLpro) has multiple functions including cleaving viral polyproteins and suppressing the host immune response by deubiquitination and deISGylation of host proteins. Inhibiting PLpro may block viral replication and help restore normal immune responses.

e. The angiotensin converting enzyme 2 (ACE2) protein is a host cell transmembrane protein that serves as the cellular receptor for the SARS-CoV-2 spike protein. ACE2 is expressed on many cell types, including epithelial cells in the lungs, and allows the virus to enter and infect host cells. Inhibition may affect ACE2's physiological function in blood pressure control.

f. Transmembrane protease serine 2 (TMPRSS2) is a host cell protease that primes the spike protein, facilitating cellular entry. TMPRSS2 activity helps enable cleavage of the spike protein required for membrane fusion and virus entry. Inhibition may especially protect respiratory epithelial cells, buy may have physiological effects.

g. The helicase, or nsp13, protein unwinds the double-stranded viral RNA, a crucial step in replication and transcription. Inhibition may prevent viral genome replication and the creation of new virus components.

h. The endoribonuclease, also known as NendoU or nsp15, cleaves specific sequences in viral RNA which may help the virus evade detection by the host immune system. Inhibition may hinder the virus's ability to mask itself from the immune system, facilitating a stronger immune response.

i. Cathepsin L is a host lysosomal cysteine protease that can prime the spike protein through an alternative pathway when TMPRSS2 is unavailable. Dual targeting of cathepsin L and TMPRSS2 may maximize disruption of alternative pathways for virus entry.

k. The frizzled (FZD) receptor is a host transmembrane receptor that binds Wnt ligands, initiating the Wnt signaling cascade. FZD serves as a co-receptor, along with ACE2, in some proposed mechanisms of SARS-CoV-2 infection. The virus may take advantage of this pathway as an alternative entry route.

l. Low-density lipoprotein receptor-related protein 6 is a cell surface co-receptor essential for Wnt signaling. LRP6 acts in tandem with FZD for signal transduction and has been discussed as a potential co-receptor for SARS-CoV-2 entry.

m. The ezrin protein links the cell membrane to the cytoskeleton (the cell's internal support structure) and plays a role in cell shape, movement, adhesion, and signaling. Drugs that occupy the same spot on ezrin where the viral spike protein would bind may hindering viral attachment, and drug binding could further stabilize ezrin, strengthening its potential natural capacity to impede viral fusion and entry.

n. The Adipocyte Differentiation-Related Protein (ADRP, also known as Perilipin 2 or PLIN2) is a lipid droplet protein regulating the storage and breakdown of fats in cells. SARS-CoV-2 may hijack the lipid handling machinery of host cells and ADRP may play a role in this process. Disrupting ADRP's interaction with the virus may hinder the virus's ability to use lipids for replication and assembly.

o. Neuropilin-1 (NRP1) is a cell surface receptor with roles in blood vessel development, nerve cell guidance, and immune responses. NRP1 may function as a co-receptor for SARS-CoV-2, facilitating viral entry into cells. Blocking NRP1 may disrupt an alternative route of viral entry.

p. EP300 (E1A Binding Protein P300) is a transcriptional coactivator involved in several cellular processes, including growth, differentiation, and apoptosis, through its acetyltransferase activity that modifies histones and non-histone proteins. EP300 facilitates viral entry into cells and upregulates inflammatory cytokine production.

q. Prostaglandin G/H synthase 2 (PTGS2, also known as COX-2) is an enzyme crucial for the production of inflammatory molecules called prostaglandins. PTGS2 plays a role in the inflammatory response that can become severe in COVID-19 and inhibitors (like some NSAIDs) may have benefits in dampening harmful inflammation, but note that prostaglandins have diverse physiological functions.

r. Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) is a chaperone protein that helps other proteins fold correctly and maintains their stability. HSP90AA1 plays roles in cell signaling, survival, and immune responses. HSP90AA1 may interact with numerous viral proteins, but note that it has diverse physiological functions.

s. Matrix metalloproteinase 9 (MMP9), also called gelatinase B, is a zinc-dependent enzyme that breaks down collagen and other components of the extracellular matrix. MMP9 levels increase in severe COVID-19. Overactive MMP9 can damage lung tissue and worsen inflammation. Inhibition of MMP9 may prevent excessive tissue damage and help regulate the inflammatory response.

t. The interleukin-6 (IL-6) pro-inflammatory cytokine (signaling molecule) has a complex role in the immune response and may trigger and perpetuate inflammation. Elevated IL-6 levels are associated with severe COVID-19 cases and cytokine storm. Anti-IL-6 therapies may be beneficial in reducing excessive inflammation in severe COVID-19 cases.

u. The interleukin-10 (IL-10) anti-inflammatory cytokine helps regulate and dampen immune responses, preventing excessive inflammation. IL-10 levels can also be elevated in severe COVID-19. IL-10 could either help control harmful inflammation or potentially contribute to immune suppression.

v. Vascular Endothelial Growth Factor A (VEGFA) promotes the growth of new blood vessels (angiogenesis) and has roles in inflammation and immune responses. VEGFA may contribute to blood vessel leakiness and excessive inflammation associated with severe COVID-19.

w. RELA is a transcription factor subunit of NF-kB and is a key regulator of inflammation, driving pro-inflammatory gene expression. SARS-CoV-2 may hijack and modulate NF-kB pathways.

x. Calu-3 is a human lung adenocarcinoma cell line with moderate ACE2 and TMPRSS2 expression and SARS-CoV-2 susceptibility. It provides a model of the human respiratory epithelium, but many not be ideal for modeling early stages of infection due to the moderate expression levels of ACE2 and TMPRSS2.

y. A549 is a human lung carcinoma cell line with low ACE2 expression and SARS-CoV-2 susceptibility. Viral entry/replication can be studied but the cells may not replicate all aspects of lung infection.

z. HEK293-ACE2+ is a human embryonic kidney cell line engineered for high ACE2 expression and SARS-CoV-2 susceptibility.

aa. Huh-7 cells were derived from a liver tumor (hepatoma).

ab. Caco-2 cells come from a colorectal adenocarcinoma (cancer). They are valued for their ability to form a polarized cell layer with properties similar to the intestinal lining.

ac. Vero E6 is an African green monkey kidney cell line with low/no ACE2 expression and high SARS-CoV-2 susceptibility. The cell line is easy to maintain and supports robust viral replication, however the monkey origin may not accurately represent human responses.

ad. mTEC is a mouse tubular epithelial cell line.

ae. RAW264.7 is a mouse macrophage cell line.

af. A mouse model expressing the human ACE2 receptor under the control of the K18 promoter.

ag. A mouse model of obesity and severe insulin resistance leading to type 2 diabetes due to a mutation in the leptin receptor gene that impairs satiety signaling.

ah. A mouse model commonly used in infectious disease and cancer research due to higher immune response and susceptibility to infection.

Alavi et al., 29 Nov 2022, Iran, peer-reviewed, 6 authors. Contact: mehranbio83@gmail.com (corresponding author), dr.m.r.mozafari@gmail.com.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Quercetin All

Interaction of Epigallocatechin Gallate and Quercetin with Spike Glycoprotein (S-Glycoprotein) of SARS-CoV-2: In Silico Study

Mehran Alavi, M R Mozafari, Saba Ghaemi, Morahem Ashengroph, Fatemeh Hasanzadeh Davarani, Mohammadreza Mohammadabadi

Biomedicines, doi:10.3390/biomedicines10123074

Severe acute respiratory syndrome (SARS)-CoV-2 from the family Coronaviridae is the cause of the outbreak of severe pneumonia, known as coronavirus disease 2019 (COVID-19), which was first recognized in 2019. Various potential antiviral drugs have been presented to hinder SARS-CoV-2 or treat COVID-19 disease. Side effects of these drugs are among the main complicated issues for patients. Natural compounds, specifically primary and secondary herbal metabolites, may be considered as alternative options to provide therapeutic activity and reduce cytotoxicity. Phenolic materials such as epigallocatechin gallate (EGCG, polyphenol) and quercetin have shown antibacterial, antifungal, antiviral, anticancer, and anti-inflammatory effects in vitro and in vivo. Therefore, in this study, molecular docking was applied to measure the docking property of epigallocatechin gallate and quercetin towards the transmembrane spike (S) glycoprotein of SARS-CoV-2. Results of the present study showed Vina scores of −9.9 and −8.3 obtained for EGCG and quercetin by CB-Dock. In the case of EGCG, four hydrogen bonds of OG1, OD2, O3, and O13 atoms interacted with the Threonine (THR778) and Aspartic acid (ASP867) amino acids of the spike glycoprotein (6VSB). According to these results, epigallocatechin gallate and quercetin can be considered potent therapeutic compounds for addressing viral diseases.

References

Ahmadi, Ahmadi, Ahmadi, A review on antifungal and antibacterial activities of some medicinal plants, Micro Nano Bio Asp

Ahmadi, Antibacterial and antifungal activities of medicinal plant species and endophytes, Cell. Mol. Biomed. Rep, doi:10.55705/cmbr.2022.340532.1042

Al-Karmalawy, Dahab, Metwaly, Elhady, Elkaeed et al., Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor, Front. Chem, doi:10.3389/fchem.2021.661230

Alavi, Adulrahman, Haleem, Al-Râwanduzi, Khusro et al., Nanoformulations of curcumin and quercetin with silver nanoparticles for inactivation of bacteria, Cell. Mol. Biol, doi:10.14715/cmb/2021.67.5.21

Alavi, Asare-Addo, Nokhodchi, Lectin Protein as a Promising Component to Functionalize Micelles, Liposomes and Lipid NPs against Coronavirus, Biomedicines, doi:10.3390/biomedicines8120580

Alavi, Hamblin, Martinez, Aghaie, Khan et al., Micro and nanoformulations of insulin: New approaches, Nano Micro Bios

Alavi, Hamblin, Martinez, Kennedy, Khan, Synergistic combinations of metal, metal oxide, or metalloid nanoparticles plus antibiotics against resistant and non-resistant bacteria, Micro Nano Bio Asp

Alavi, Hamblin, Mozafari, Rose Alencar De Menezes, Douglas Melo Coutinho, Surface modification of SiO 2 nanoparticles for bacterial decontaminations of blood products, Cell. Mol. Biomed. Rep, doi:10.55705/cmbr.2022.338888.1039

Alavi, Kowalski, Capasso, Douglas Melo Coutinho, Rose Alencar De Menezes, Various novel strategies for functionalization of gold and silver nanoparticles to hinder drug-resistant bacteria and cancer cells, Micro Nano Bio Asp

Alavi, Martinez, Delgado, Tinjacá, Anticancer and antibacterial activities of embelin: Micro and nano aspects, Micro Nano Bio Asp

Alavi, Rai, Antisense RNA, the modified CRISPR-Cas9, and metal/metal oxide nanoparticles to inactivate pathogenic bacteria, Cell. Mol. Biomed. Rep, doi:10.55705/cmbr.2021.142436.1014

Alavi, Rai, Martinez, Kahrizi, Khan et al., The efficiency of metal, metal oxide, and metalloid nanoparticles against cancer cells and bacterial pathogens: Different mechanisms of action, Cell. Mol. Biomed. Rep, doi:10.55705/cmbr.2022.147090.1023

Alavi, Thomas, Sreedharan, Modification of silica nanoparticles for antibacterial activities: Mechanism of action, Micro Nano Bio Asp

Albuquerque, Heleno, Oliveira, Barros, Ferreira, Phenolic compounds: Current industrial applications, limitations and future challenges, Food Funct, doi:10.1039/D0FO02324H

Aljelehawy, Alshaibah, Khafaji, Evaluation of virulence factors among Staphylococcus aureus strains isolated from patients with urinary tract infection in Al-Najaf Al-Ashraf teaching hospital, Cell. Mol. Biomed. Rep

Almasian-Tehrani, Alebouyeh, Armin, Soleimani, Azimi et al., Overview of typing techniques as molecular epidemiology tools for bacterial characterization, Cell. Mol. Biomed. Rep, doi:10.55705/cmbr.2021.143413.1016

Amraei, Ahmadi, Recent studies on antimicrobial and anticancer activities of saponins: A mini-review, Nano Micro Bios

Andijani, Wazzan, The effect of electron-donating substituents on tuning the nonlinear optical properties of pyrene-core arylamine derivatives: DFT calculations, Results Phys, doi:10.1016/j.rinp.2018.10.002

Arévalo, Pagotto, Pórfido, Daghero, Segovia et al., Ivermectin reduces in vivo coronavirus infection in a mouse experimental model, Sci. Rep, doi:10.1038/s41598-021-86679-0

Baral, Mozafari, Strategic Moves of "Superbugs" Against Available Chemical Scaffolds: Signaling, Regulation, and Challenges, ACS Pharmacol. Transl. Sci, doi:10.1021/acsptsci.0c00005

Basu, Sarkar, Maulik, Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2, Sci. Rep, doi:10.1038/s41598-020-74715-4

Cao, Li, Improved protein-ligand binding affinity prediction by using a curvature-dependent surface-area model, Bioinformatics, doi:10.1093/bioinformatics/btu104

Casas-Sanchez, Romero-Ramirez, Hargreaves, Ellis, Grajeda et al., Inhibition of Protein N-Glycosylation Blocks SARS-CoV-2 Infection, mBio

Ceccarelli, Alessandri, Oliva, Borrazzo, Dell'isola et al., The role of teicoplanin in the treatment of SARS-CoV-2 infection: A retrospective study in critically ill COVID-19 patients (Tei-COVID study), J. Med. Virol, doi:10.1002/jmv.26925

Chamkhi, Benali, Aanniz, El Menyiy, Guaouguaou et al., Plant-microbial interaction: The mechanism and the application of microbial elicitor induced secondary metabolites biosynthesis in medicinal plants, Plant Physiol. Biochem, doi:10.1016/j.plaphy.2021.08.001

Choudhary, Zehra, Mukarram, Wani, Naeem et al., Potential Uses of Bioactive Compounds of Medicinal Plants and Their Mode of Action in Several Human Diseases

De Maat, Pijl, Kluft, Princen, Consumption of black and green tea had no effect on inflammation, haemostasis and endothelial markers in smoking healthy individuals, Eur. J. Clin. Nutr, doi:10.1038/sj.ejcn.1601084

Du, Zheng, Disoma, Li, Chen et al., Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2, Int. J. Biol. Macromol

Eberhardt, Santos-Martins, Tillack, Forli, AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings, J. Chem. Inf. Model, doi:10.1021/acs.jcim.1c00203

Eweas, Alhossary, Abdel-Moneim, Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2, Front. Microbiol, doi:10.3389/fmicb.2020.592908

Fischer, Müller, Scheidt, Luck, Drug-Membrane Interactions: Effects of Virus-Specific RNA-Dependent RNA Polymerase Inhibitors Remdesivir and Favipiravir on the Structure of Lipid Bilayers, Biochemistry, doi:10.1021/acs.biochem.2c00042

Gasmi, Mujawdiya, Lysiuk, Shanaida, Peana et al., Quercetin in the Prevention and Treatment of Coronavirus Infections: A Focus on SARS-CoV-2, Pharmaceuticals, doi:10.3390/ph15091049

Golonka, Wilk, Musiał, The Influence of UV Radiation on the Degradation of Pharmaceutical Formulations Containing Quercetin, Molecules, doi:10.3390/molecules25225454

Guedes, Costa, Dos Santos, Karl, Rocha et al., Drug design and repurposing with DockThor-VS web server focusing on SARS-CoV-2 therapeutic targets and their non-synonym variants, Sci. Rep, doi:10.1038/s41598-021-84700-0

Han, Ren, Li, Yan, Ma et al., Advances and challenges in the prevention and treatment of COVID-19, Int. J. Med. Sci, doi:10.7150/ijms.47836

Hashemzaei, Delarami Far, Yari, Heravi, Tabrizian et al., Anticancer and apoptosis-inducing effects of quercetin in vitro and in vivo, Oncol. Rep, doi:10.3892/or.2017.5766

Hong, Seo, Woo, Kwon, Song et al., Epigallocatechin Gallate Inhibits the Uridylate-Specific Endoribonuclease Nsp15 and Efficiently Neutralizes the SARS-CoV-2 Strain, J. Agric. Food Chem, doi:10.1021/acs.jafc.1c02050

Isbrucker, Edwards, Wolz, Davidovich, Bausch, Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: Dermal, acute and short-term toxicity studies, Food Chem. Toxicol, doi:10.1016/j.fct.2005.11.003

Joshi, Parkar, Ansari, Vora, Talwar et al., Role of favipiravir in the treatment of COVID-19, Int. J. Infect. Dis, doi:10.1016/j.ijid.2020.10.069

Kabarkouhi, Mehrarya, Gharehchelou, Jalilian, Jalili et al., Nanoliposome and Allied Technologies in COVID-19 Vaccines: Key Roles and Functionalities, Curr. Drug Deliv, doi:10.2174/1567201819666220427125342

Kawano, Hwang, Influence of Guanidine, Imidazole, and Some Heterocyclic Compounds on Dissolution Rates of Amorphous Silica, Clays Clay Miner, doi:10.1346/CCMN.2010.0580603

Kivrak, Ulaş, Kivrak, A comparative analysis for anti-viral drugs: Their efficiency against SARS-CoV-2, Int. Immunopharmacol, doi:10.1016/j.intimp.2020.107232

Komeno, Furuta, Nakajima, Tani, Morinaga, Analysis of the responsible site for favipiravir resistance in RNA-dependent RNA polymerase of influenza virus A/PR/8/34 (H1N1) using site-directed mutagenesis, Antivir. Res, doi:10.1016/j.antiviral.2022.105387

Kournoutou, Dinos, Azithromycin through the Lens of the COVID-19 Treatment, Antibiotics, doi:10.3390/antibiotics11081063

Liu, Grimm, Dai, Hou, Xiao et al., CB-Dock: A web server for cavity detection-guided protein-ligand blind docking, Acta Pharmacol. Sin, doi:10.1038/s41401-019-0228-6

Lopes, Da Costa, Genova Ribeiro, Da Silva, Lima et al., Quercetin pentaacetate inhibits in vitro human respiratory syncytial virus adhesion, Virus Res, doi:10.1016/j.virusres.2019.197805

Maiti, Banerjee, Epigallocatechin gallate and theaflavin gallate interaction in SARS-CoV-2 spike-protein central channel with reference to the hydroxychloroquine interaction: Bioinformatics and molecular docking study, Drug Dev. Res, doi:10.1002/ddr.21730

Majumder, Taufiqur Rahman, Mahedi Hasan, Didarul Islam, Taylor-Robinson et al., Decoding the enigma of antiviral crisis: Does one target molecule regulate all?, Cytokine, doi:10.1016/j.cyto.2018.12.008

Mettelman, Allen, Thomas, Mucosal immune responses to infection and vaccination in the respiratory tract, Immunity, doi:10.1016/j.immuni.2022.04.013

Mirtaleb, Mirtaleb, Nosrati, Heshmatnia, Falak et al., Potential therapeutic agents to COVID-19: An update review on antiviral therapy, immunotherapy, and cell therapy, Biomed. Pharmacother

Mohammadi, Sabati, When Successive Viral Mutations Prevent Definitive Treatment of COVID-19, Cell. Mol. Biomed. Rep, doi:10.55705/cmbr.2022.339012.1040

Mozafari, Torkaman, Karamouzian, Rasti, Baral, Antimicrobial Applications of Nanoliposome Encapsulated Silver Nanoparticles: A Potential Strategy to Overcome Bacterial Resistance, Curr. Nanosci, doi:10.2174/1573413716999200712184148

Mpiana, Ngbolua, Tshibangu, Kilembe, Gbolo et al., Identification of potential inhibitors of SARS-CoV-2 main protease from Aloe vera compounds: A molecular docking study, Chem. Phys. Lett, doi:10.1016/j.cplett.2020.137751

Muhammad, Abubakar, Muhammad, Genetic resistance to human malaria, Cell. Mol. Biomed. Rep

Muhammad, Sale, Salisu, Muhammad, Abubakar et al., Molecular analysis of Bio-makers of Chloroquine resistance in Plasmodium falciparum Isolate from Gombe Local Government Area, Gombe State, Nigeria, Cell. Mol. Biomed. Rep, doi:10.55705/cmbr.2022.335753.1033

Murad, Alqurashi, Hussien, Interactions of selected cardiovascular active natural compounds with CXCR4 and CXCR7 receptors: A molecular docking, molecular dynamics, and pharmacokinetic/toxicity prediction study, BMC Complement. Med. Ther, doi:10.1186/s12906-021-03488-8

Narendrakumar, Joseph, Thomas, Potential effectiveness and adverse implications of repurposing doxycycline in COVID-19 treatment, Expert Rev. Anti-Infect. Ther, doi:10.1080/14787210.2021.1865803

Nguyen, Woo, Kang, Nguyen, Kim et al., Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris, Biotechnol. Lett, doi:10.1007/s10529-011-0845-8

Ntamo, Jack, Ziqubu, Mazibuko-Mbeje, Nkambule et al., Epigallocatechin gallate as a nutraceutical to potentially target the metabolic syndrome: Novel insights into therapeutic effects beyond its antioxidant and anti-inflammatory properties, Crit. Rev. Food Sci. Nutr, doi:10.1080/10408398.2022.2104805

Pillon, Frazier, Dillard, Williams, Kocaman et al., Cryo-EM Structures of the SARS-CoV-2 Endoribonuclease Nsp15, Biorxiv Prepr. Serv. Biol, doi:10.1101/2020.08.11.244863

Puttaswamy, Gowtham, Ojha, Yadav, Choudhir et al., In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis, Sci. Rep, doi:10.1038/s41598-020-77602-0

Quinn, Patel, Koh, Haines, Norrby et al., Automated fitting of transition state force fields for biomolecular simulations, PLoS ONE, doi:10.1371/journal.pone.0264960

Rahbar-Karbasdehi, Rahbar-Karbasdehi, Clinical challenges of stress cardiomyopathy during coronavirus 2019 epidemic, Cell. Mol. Biomed. Rep, doi:10.55705/cmbr.2021.145790.1018

Rahman, Tabrez, Ali, Alqahtani, Ahmed et al., Molecular docking analysis of rutin reveals possible inhibition of SARS-CoV-2 vital proteins, J. Tradit. Complement. Med, doi:10.1016/j.jtcme.2021.01.006

Sabbagh, Kiarostami, Khatir, Rezania, Muhamad et al., Effect of zinc content on structural, functional, morphological, and thermal properties of kappa-carrageenan/NaCMC nanocomposites, Polym. Test, doi:10.1016/j.polymertesting.2020.106922

Sabbagh, Kiarostami, Mahmoudi Khatir, Rezania, Muhamad, Green Synthesis of Mg0.99 Zn0.01O Nanoparticles for the Fabrication of κ-Carrageenan/NaCMC Hydrogel in order to Deliver Catechin, Polymers, doi:10.3390/polym12040861

Salehi, Machin, Monzote, Sharifi-Rad, Ezzat et al., Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health, ACS Omega, doi:10.1021/acsomega.0c01818

Samy, Attia, Shoman, Khalil, Sugimoto et al., Phytochemical investigation of Amphilophium paniculatum; an underexplored Bignoniaceae species as a source of SARS-CoV-2 Mpro inhibitory metabolites: Isolation, identification, and molecular docking study, S. Afr. J. Bot, doi:10.1016/j.sajb.2021.05.023

Santos, Brierley, Gandhi, Cohen, Moschella et al., Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review, Viruses, doi:10.3390/v12070705

Santos, Grosche, Bergamini, Sabino-Silva, Jardim, Antivirals Against Coronaviruses: Candidate Drugs for SARS-CoV-2 Treatment? Front, Microbiol, doi:10.3389/fmicb.2020.01818

Schmitz, Gilberg, Löser, Bajorath, Bartz et al., Cathepsin B: Active site mapping with peptidic substrates and inhibitors, Biorg. Med. Chem, doi:10.1016/j.bmc.2018.10.017

Shehata, Attia, Rahman, Basiouni, El-Seedi et al., Diversity of Coronaviruses with Particular Attention to the Interspecies Transmission of SARS-CoV-2, Animals, doi:10.3390/ani12030378

Singh, Chapter 11-Molecular modeling studies of fused pyrimidine derivatives at various receptors, doi:10.1016/B978-0-443-18616-5.00010-7

Sun, Gao, Hu, Zhou, Why 90% of clinical drug development fails and how to improve it?, Acta Pharm. Sin. B, doi:10.1016/j.apsb.2022.02.002

Taguchi, Turki, A new advanced in silico drug discovery method for novel coronavirus (SARS-CoV-2) with tensor decomposition-based unsupervised feature extraction, PLoS ONE, doi:10.1371/journal.pone.0238907

Tamimi, Altigani, Sanz, Periodontitis and coronavirus disease 2019, Periodontol, doi:10.1111/prd.12434

Tripathy, Dassarma, Roy, Chabalala, Matsabisa, A review on possible modes of action of chloroquine/hydroxychloroquine: Repurposing against SAR-CoV-2 (COVID-19) pandemic, Int. J. Antimicrob. Agents

Uzunova, Filipova, Pavlova, Vekov, Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2, Biomed. Pharmacother, doi:10.1016/j.biopha.2020.110668

Verma, Patel, Chandra, Identification of novel inhibitors of SARS-CoV-2 main protease (Mpro) from Withania sp. by molecular docking and molecular dynamics simulation, J. Comput. Chem, doi:10.1002/jcc.26717

Vicenti, Zazzi, Saladini, SARS-CoV-2 RNA-dependent RNA polymerase as a therapeutic target for COVID-19, Expert Opin. Ther. Pat, doi:10.1080/13543776.2021.1880568

Yang, Atkinson, Wang, Lee, Bogoyevitch et al., The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer, Antivir. Res, doi:10.1016/j.antiviral.2020.104760

Yang, Guo, Yu, Liu, Song et al., Tocilizumab mimotope alleviates kidney injury and fibrosis by inhibiting IL-6 signaling and ferroptosis in UUO model, Life Sci, doi:10.1016/j.lfs.2020.118487

Yang, Petitjean, Koehler, Zhang, Dumitru et al., Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor, Nat. Commun, doi:10.1038/s41467-020-18319-6

Yang, Wei, Fang, Gan, Wang et al., Nanochemoprevention with therapeutic benefits: An updated review focused on epigallocatechin gallate delivery, Crit. Rev. Food Sci. Nutr

Yi, Peng, Wu, Xu, Kuang et al., The Therapeutic Effects and Mechanisms of Quercetin on Metabolic Diseases: Pharmacological Data and Clinical Evidence, Oxid. Med. Cell. Longev, doi:10.1155/2021/6678662

Zhang, Bell, Yin, Zhang, EDock: Blind protein-ligand docking by replica-exchange monte carlo simulation, J. Cheminform, doi:10.1186/s13321-020-00440-9

Zhu, Guo, Geary, Zhang, Emerging Therapeutic Strategies for COVID-19 patients, Discoveries, doi:10.15190/d.2020.2

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