Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2

Kandeil et al., Pathogens, doi:10.3390/pathogens10060758

Jun 2021

Source PDF All Studies Meta AnalysisMeta

Vero E6 In Vitro study showing curcumin, hesperidin, and quercetin significantly inhibited SARS-CoV-2 replication, and In Silico analysis with promising M^pro and spike docking results.

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

14 In Silico studies Alavi, Azmi, Chellasamy, Corbo, Ibeh, Kandeil, Mandal, Nguyen, Sai Ramesh, Sekiou, Thapa, Wang, Yang, Şimşek

7 In Vitro studies Aguado, Bahun, Goc, Kandeil, Munafò, Singh, Xu

2 In Vivo animal studies Aguado, Wu

Important missing comments or errors? Let us know.

This study includes curcumin and quercetin.

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. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. Singh 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.

17. 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.

18. 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.

19. Wu 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.

20. 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.

21. Yang 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.

Kandeil et al., 15 Jun 2021, peer-reviewed, 11 authors.

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

All Studies Meta Analysis Submit Updates or Corrections

This Paper Quercetin All

Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2

Ahmed Kandeil, Ahmed Mostafa, Omnia Kutkat, Yassmin Moatasim, Ahmed A Al-Karmalawy, Adel A Rashad, Ahmed E Kayed, Azza E Kayed, Rabeh El-Shesheny, Ghazi Kayali, Mohamed A Ali

Pathogens, doi:10.3390/pathogens10060758

Until now, there has been no direct evidence of the effectiveness of repurposed FDAapproved drugs against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections. Although curcumin, hesperidin, and quercetin have broad spectra of pharmacological properties, their antiviral activities against SARS-CoV-2 remain unclear. Our study aimed to assess the in vitro antiviral activities of curcumin, hesperidin, and quercetin against SARS-CoV-2 compared to hydroxychloroquine and determine their mode of action. In Vero E6 cells, these compounds significantly inhibited virus replication, mainly as virucidal agents primarily indicating their potential activity at the early stage of viral infection. To investigate the mechanism of action of the tested compounds, molecular docking studies were carried out against both SARS-CoV-2 spike (S) and main protease (Mpro) receptors. Collectively, the obtained in silico and in vitro findings suggest that the compounds could be promising SARS-CoV-2 Mpro inhibitors. We recommend further preclinical and clinical studies on the studied compounds to find a potential therapeutic targeting COVID-19 in the near future.

Data Availability Statement: The data presented in this study are available within the article and Supplementary Materials. Conflicts of Interest: The authors declare no conflict of interest.

References

Abouaitah, Swiderska-Sroda, Kandeil, Salman, Wojnarowicz et al., Virucidal Action Against Avian Influenza H5N1 Virus and Immunomodulatory Effects of Nanoformulations Consisting of Mesoporous Silica Nanoparticles Loaded with Natural Prodrugs, Int. J. Nanomed, doi:10.2147/IJN.S247692

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

Al-Karmalawy, Eissa, Molecular docking and dynamics simulations reveal the potential of anti-HCV drugs to inhibit COVID-19 main protease, Pharm. Sci, doi:10.34172/PS.2021.3

Al-Karmalawy, Khattab, Molecular modelling of mebendazole polymorphs as a potential colchicine binding site inhibitor, New J. Chem, doi:10.1039/D0NJ02844D

Alnajjar, Mostafa, Kandeil, Al-Karmalawy, Molecular docking, molecular dynamics, and in vitro studies reveal the potential of angiotensin II receptor blockers to inhibit the COVID-19 main protease, Heliyon, doi:10.1016/j.heliyon.2020.e05641

Annunziata, Zamparelli, Santoro, Ciampaglia, Stornaiuolo et al., May Polyphenols Have a Role Against Coronavirus Infection? An Overview of in vitro Evidence, Front. Med, doi:10.3389/fmed.2020.00240

Brogi, Computational Approaches for Drug Discovery, Molecules, doi:10.3390/molecules24173061

Chen, Chen, Wen, Ou, Chiou et al., Inhibition of Enveloped Viruses Infectivity by Curcumin, PLoS ONE, doi:10.1371/journal.pone.0062482

Choi, Song, Park, Kwon, Inhibitory effects of quercetin 3-rhamnoside on influenza A virus replication, Eur. J. Pharm. Sci, doi:10.1016/j.ejps.2009.03.002

Chu, Pan, Cheng, Hui, Krishnan et al., Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia, Clin. Chem, doi:10.1093/clinchem/hvaa029

Colpitts, Schang, Rachmawati, Frentzen, Pfaender et al., Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells, Gut

Dong, Wei, Zhang, Hao, Huang et al., A dual character of flavonoids in influenza A virus replication and spread through modulating cell-autonomous immunity by MAPK signaling pathways, Sci. Rep, doi:10.1038/srep07237

El Shal, Eid, El-Sayed, El-Sayed, Al-Karmalawy, Concanavalin-A shows synergistic cytotoxicity with tamoxifen via inducing apoptosis in estrogen receptor-positive breast cancer: In vitro and molecular docking studies, Pharm. Sci, doi:10.34172/PS.2021.22

Eliaa, Al-Karmalawy, Saleh, Elshal, Empagliflozin and Doxorubicin Synergistically Inhibit the Survival of Triple-Negative Breast Cancer Cells via Interfering with the mTOR Pathway and Inhibition of Calmodulin: In Vitro and Molecular Docking Studies, ACS Pharmacol. Transl. Sci, doi:10.1021/acsptsci.0c00144

Elmaaty, Alnajjar, Hamed, Khattab, Khalifa et al., Revisiting activity of some glucocorticoids as a potential inhibitor of SARS-CoV-2 main protease: Theoretical study, RSC Adv, doi:10.1039/D0RA10674G

Elmaaty, Darwish, Khattab, Elhady, Salah et al., In a search for potential drug candidates for combating COVID-19: Computational study revealed salvianolic acid B as a potential therapeutic targeting 3CLpro and spike proteins, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2021.1918256

Gao, Wang, Wei, Men, Zheng et al., Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer, Nanoscale, doi:10.1039/c2nr32181e

Ghanem, Emara, Muawia, El Maksoud, Al-Karmalawy et al., Tanshinone IIA synergistically enhances the antitumor activity of doxorubicin by interfering with the PI3K/AKT/mTOR pathway and inhibition of topoisomerase II: In vitro and molecular docking studies, New J. Chem, doi:10.1039/D0NJ04088F

Guedes, De Magalhães, Dardenne, Receptor-ligand molecular docking, Biophys. Rev, doi:10.1007/s12551-013-0130-2

Haggag, El-Ashmawy, Okasha, Is hesperidin essential for prophylaxis and treatment of COVID-19 Infection?, Med. Hypotheses, doi:10.1016/j.mehy.2020.109957

Hajialyani, Farzaei, Echeverría, Nabavi, Uriarte et al., Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence, Molecules, doi:10.3390/molecules24030648

Harwood, Danielewska-Nikiel, Borzelleca, Flamm, Williams et al., A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties, Food Chem. Toxicol, doi:10.1016/j.fct.2007.05.015

Jin, Du, Xu, Deng, Liu et al., Structure of M pro from SARS-CoV-2 and discovery of its inhibitors, Nature, doi:10.1038/s41586-020-2223-y

Johari, Kianmehr, Mustafa, Abubakar, Zandi, Antiviral activity of baicalein and quercetin against the Japanese encephalitis virus, Int. J. Mol. Sci, doi:10.3390/ijms131216785

Khattab, Al-Karmalawy, Revisiting Activity of Some Nocodazole Analogues as a Potential Anticancer Drugs Using Molecular Docking and DFT Calculations, Front. Chem, doi:10.3389/fchem.2021.628398

Kim, Kim, Song, Antiviral Activities of Quercetin and Isoquercitrin Against Human Herpesviruses, Molecules, doi:10.3390/molecules25102379

Kobayashi, Tanabe, Sugiyama, Konishi, Transepithelial transport of hesperetin and hesperidin in intestinal Caco-2 cell monolayers, Biochim. Biophys. Acta (BBA) Biomembr, doi:10.1016/j.bbamem.2007.08.020

Kuo, Lin, Tsai, Chou, Kung et al., Samarangenin B from Limonium sinense Suppresses Herpes Simplex Virus Type 1 Replication in Vero Cells by Regulation of Viral Macromolecular Synthesis, Antimicrob. Agents Chemother, doi:10.1128/AAC.46.9.2854-2864.2002

Li, Xu, Quercetin in a lotus leaves extract may be responsible for antibacterial activity, Arch. Pharmacal Res, doi:10.1007/s12272-001-1206-5

Maheshwari, Singh, Gaddipati, Srimal, Multiple biological activities of curcumin: A short review, Life Sci, doi:10.1016/j.lfs.2005.12.007

Mazumder, Raghavan, Weinstein, Kohn, Pommier, Inhibition of human immunodeficiency virus type-1 integrase by curcumin, Biochem. Pharmacol, doi:10.1016/0006-2952(95)98514-A

Moghadamtousi, Kadir, Hassandarvish, Tajik, Abubakar et al., A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin, BioMed Res. Int, doi:10.1155/2014/186864

Mosmann, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, J. Immunol. Methods, doi:10.1016/0022-1759(83)90303-4

Mostafa, Kandeil, Elshaier, Kutkat, Moatasim et al., FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2, Pharmaceuticals, doi:10.3390/ph13120443

Mounce, Cesaro, Carrau, Vallet, Vignuzzi, Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding, Antivir. Res, doi:10.1016/j.antiviral.2017.03.014

Nabila, Suada, Denis, Yohan, Adi et al., Antiviral Action of Curcumin Encapsulated in Nanoemulsion against Four Serotypes of Dengue Virus, Pharm. Nanotechnol, doi:10.2174/2211738507666191210163408

Orfali, Rateb, Hassan, Alonazi, Gomaa et al., Sinapic Acid Suppresses SARS CoV-2 Replication by Targeting Its Envelope Protein, Antibiotics, doi:10.3390/antibiotics10040420

Parvez, Rehman, Alam, Al-Dosari, Alqasoumi et al., Plant-derived antiviral drugs as novel hepatitis B virus inhibitors: Cell culture and molecular docking study, Saudi Pharm. J, doi:10.1016/j.jsps.2018.12.008

Prasad, Gupta, Tyagi, Aggarwal, Curcumin, a component of golden spice: From bedside to bench and back, Biotechnol. Adv, doi:10.1016/j.biotechadv.2014.04.004

Robaszkiewicz, Balcerczyk, Bartosz, Antioxidative and prooxidative effects of quercetin on A549 cells, Cell Biol. Int, doi:10.1016/j.cellbi.2007.04.009

Rojas, Del Campo, Clement, Lemasson, García-Valdecasas et al., Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets, Sci. Rep, doi:10.1038/srep31777

Roshdy, Rashed, Kandeil, Mostafa, Moatasim et al., EGYVIR: An immunomodulatory herbal extract with potent antiviral activity against SARS-CoV-2, PLoS ONE, doi:10.1371/journal.pone.0241739

Samra, Soliman, Zaki, Ashour, Al-Karmalawy et al., Bioassay-guided isolation of a new cytotoxic ceramide from Cyperus rotundus L, S. Afr. J. Bot, doi:10.1016/j.sajb.2021.02.007

Sarhan, Ashour, Al-Karmalawy, The journey of antimalarial drugs against SARS-CoV-2: Review article, Inform. Med. Unlocked, doi:10.1016/j.imu.2021.100604

Schuhmacher, Reichling, Schnitzler, Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro, Phytomedicine, doi:10.1078/094471103322331467

Shang, Ye, Shi, Wan, Luo et al., Structural basis of receptor recognition by SARS-CoV-2, Nature, doi:10.1038/s41586-020-2179-y

Soltane, Chrouda, Mostafa, Al-Karmalawy, Chouaïb et al., Strong Inhibitory Activity and Action Modes of Synthetic Maslinic Acid Derivative on Highly Pathogenic Coronaviruses: COVID-19 Drug Candidate, Pathogens, doi:10.3390/pathogens10050623

Swatson, Katoh-Kurasawa, Shaulsky, Alexander, Curcumin affects gene expression and reactive oxygen species via a PKA dependent mechanism in Dictyostelium discoideum, PLoS ONE, doi:10.1371/journal.pone.0187562

Vázquez-Calvo, De Oya, Martín-Acebes, Garcia-Moruno, Saiz, Antiviral Properties of the Natural Polyphenols Delphinidin and Epigallocatechin Gallate against the Flaviviruses West Nile Virus, Zika Virus, and Dengue Virus, Front. Microbiol, doi:10.3389/fmicb.2017.01314

Wu, Hou, Cao, Zuo, Xue et al., Virucidal efficacy of treatment with photodynamically activated curcumin on murine norovirus bio-accumulated in oysters, Photodiagn. Photodyn. Ther, doi:10.1016/j.pdpdt.2015.06.005

Wu, Li, Li, He, Jiang et al., Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry, Viruses, doi:10.3390/v8010006

Wu, Liu, Yang, Zhang, Zhong et al., Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharm. Sin. B, doi:10.1016/j.apsb.2020.02.008

Yang, Lee, Si, Lee, You et al., Curcumin Shows Antiviral Properties against Norovirus, Molecules, doi:10.3390/molecules21101401

Yang, Li, Li, Wang, Huang, Synergistic antiviral effect of curcumin functionalized graphene oxide against respiratory syncytial virus infection, Nanoscale, doi:10.1039/C7NR06520E

Zaki, Al-Karmalawy, El-Amier, Ashour, Molecular docking reveals the potential of Cleome amblyocarpa isolated compounds to inhibit COVID-19 virus main protease, New J. Chem, doi:10.1039/D0NJ03611K

Zaki, Ashour, Elhady, Darwish, Al-Karmalawy, Calendulaglycoside A Showing Potential Activity Against SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and SAR Studies, J. Tradit. Complement. Med

Zhang, Zhan, Yao, Gao, Shong, Antiviral activity of tannin from the pericarp of Punica granatum L. against genital Herpes virus in vitro, China J. Chin. Mater. Med

Download Image

Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Submit

@CovidAnalysis

FAQ

Public domain CC0 1.0