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All Studies   Meta Analysis    Recent:   

Quercetin inhibits SARS-CoV-2 infection and prevents syncytium formation by cells co-expressing the viral spike protein and human ACE2

Roy et al., Virology Journal, doi:10.1186/s12985-024-02299-w
Jan 2024  
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Quercetin for COVID-19
24th treatment shown to reduce risk in July 2021
 
*, now known with p = 0.0031 from 11 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
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In Vitro study showing inhibition of SARS-CoV-2 infection and syncytium formation by quercetin in Vero E6 and Caco-2 cells at 100-400μM concentrations. Authors found that quercetin prevented the proteolytic processing of the SARS-CoV-2 spike protein required for cell fusion, potentially by inhibiting the furin protease responsible for this cleavage. Quercetin also directly inhibited furin activity. The results suggest that sufficiently bioavailable formulations of quercetin may impair viral propagation mechanisms and be a potential COVID-19 treatment.
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, Mpro Note B, Akinwumi, Alanzi, Ibeh, Kandeil, Mandal, Moschovou, Nguyen, Qin, Rehman, Sekiou (B), Singh, Thapa (B), Wang, Zhang, 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, PTGS2 Note P, Qin, HSP90AA1 Note Q, Qin, matrix metalloproteinase 9 Note R, Sai Ramesh, IL-6 Note S, Yang, Yang (B), IL-10 Note T, Yang, VEGFA Note U, Yang (B), and RELA Note V, Yang (B) proteins. In Vitro studies demonstrate efficacy in Calu-3 Note W, DiGuilio, A549 Note X, Yang, HEK293-ACE2+ Note Y, Singh (C), Huh-7 Note Z, Pan, Caco-2 Note AA, Roy, Vero E6 Note AB, Kandeil, El-Megharbel, Roy, mTEC Note AC, Wu, and RAW264.7 Note AD, Wu cells. Animal studies demonstrate efficacy in K18-hACE2 mice Note AE, Aguado, rats El-Megharbel (B), and db/db mice Note AF, Wu, Wu (B).
Roy et al., 25 Jan 2024, peer-reviewed, 7 authors. Contact: majambu.mbikay@ircm.qc.ca.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperQuercetinAll
Quercetin inhibits SARS-CoV-2 infection and prevents syncytium formation by cells co-expressing the viral spike protein and human ACE2
Annie V Roy, Michael Chan, Logan Banadyga, Shihua He, Wenjun Zhu, Michel Chrétien, Majambu Mbikay
Virology Journal, doi:10.1186/s12985-024-02299-w
Background Several in silico studies have determined that quercetin, a plant flavonol, could bind with strong affinity and low free energy to SARS-CoV-2 proteins involved in viral entry and replication, suggesting it could block infection of human cells by the virus. In the present study, we examined the ex vivo ability of quercetin to inhibit of SARS-CoV-2 replication and explored the mechanisms of this inhibition. Methods Green monkey kidney Vero E6 cells and in human colon carcinoma Caco-2 cells were infected with SARS-CoV-2 and incubated in presence of quercetin; the amount of replicated viral RNA was measured in spent media by RT-qPCR. Since the formation of syncytia is a mechanism of SARS-CoV-2 propagation, a syncytialization model was set up using human embryonic kidney HEK293 co-expressing SARS-CoV-2 Spike (S) protein and human angiotensin converting enzyme 2 (ACE2), [HEK293(S + ACE2) cells], to assess the effect of quercetin on this cytopathic event by microscopic imaging and protein immunoblotting. Results Quercetin inhibited SARS-CoV-2 replication in Vero E6 cells and Caco-2 cells in a concentration-dependent manner with a half inhibitory concentration (IC 50 ) of 166.6 and 145.2 µM, respectively. It also inhibited syncytialization of HEK293(S + ACE2) cells with an IC 50 of 156.7 µM. Spike and ACE2 co-expression was associated with decreased expression, increased proteolytic processing of the S protein, and diminished production of the fusogenic S2' fragment of S. Furin, a proposed protease for this processing, was inhibited by quercetin in vitro with an IC 50 of 116 µM. Conclusion These findings suggest that at low 3-digit micromolar concentrations of quercetin could impair SARS-CoV-2 infection of human cells partly by blocking the fusion process that promotes its propagation.
Abbreviations Supplementary Information The online version contains supplementary material available at https://doi. org/10.1186/s12985-024-02299-w. Supplementary Material 1: Supplementary Figure S1 . Confirmation of S protein bands. Cells were transfected with the indicated expression vectors and their extracts analyzed as described for Fig. 3 . Immunoblotting of S protein and its fragments was performed using antibodies from Abcam (cat# ab272504) and Sino Biological (cat# 40592-T62). The Spike-Linker-GFP gene is expressed as a fusion S-GFP protein whereas with the Spike-P2A-GFP gene, the S protein and GFP are expressed as two separate molecules, hence the size difference in immunoreactive S bands produced par the two vectors. Supplementary Material 2: Supplementary Figure S2 . Pull-down of ACE2 by S protein. HEK293(S+ACE2) cell extracts were subjected to immunoprecipitation with GFP-trap beads. The precipitates were analyzed by immunoblotting for ACE-2 and GFP; the densities of immunoreactive bands were determined. A. A representative blot. B&C. The S/ACE2 and S2/ACE density ratios were computed. The values (means ± SD of 3 independent experiments) of quercetin-treated cells were expressed relative to those of DMSO treated control cells. Supplementary Material 3: Supplementary Figure S3 . Effect of isoquercetin on HEK293(S+ACE2) syncytialization. The experiment was conducted as described in Fig. 1 . Isoquercetin did not inhibit the formation de syncytia...
References
Abian, Ortega-Alarcon, Jimenez-Alesanco, Ceballos-Laita, Vega et al., Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening, Int J Biol Macromol
Babadaei, Hasan, Vahdani, Bloukh, Sharifi et al., Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase, J Biomol Struct Dyn
Buchrieser, Dufloo, Hubert, Monel, Planas et al., Syncytia formation by SARS-CoV-2-infected cells, EMBO J
Carullo, Badolato, Aiello, Bioavailability and biochemistry of quercetin and applications to health and diseases
Chaves, Fintelman-Rodrigues, Wang, Sacramento, Temerozo et al., Commercially available flavonols are better SARS-CoV-2 inhibitors than isoflavone and Flavones, Viruses
De Boer, Dihal, Van Der Woude, Arts, Wolffram et al., Tissue distribution of quercetin in rats and pigs, J Nutr
De Granada-Flor, Sousa, Filipe, Santos, De Almeida, Quercetin dual interaction at the membrane level, ChemComm
Donnelly, Luke, Mehrotra, Li, Hughes et al., Analysis of the aphthovirus 2A/2B polyprotein 'cleavage' mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal 'skip, J Gen Virol
Essalmani, Jain, Resiga, Andreo, Evagelidis et al., Distinctive roles of furin and TMPRSS2 in SARS-CoV-2 infectivity, J Virol
Fodor, Tiperciuc, Login, Orasan, Lazar et al., Endothelial dysfunction, inflammation, and oxidative stress in COVID-19-mechanisms and therapeutic targets, Oxid Med Cell Longev
Furushima, Otake, Koike, Onishi, Mori et al., Investigation of the oral Retention of Tea catechins in humans: an exploratory interventional study, Nutrients
Ganguli, Howlader, Dey, Barua, Islam et al., Association of comorbidities with the COVID-19 severity and hospitalization: a study among the recovered individuals in Bangladesh, Int J Health Sci
Garcia-Albeniz, Amo, Polo, Morales-Asencio, Hernan, Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19, Eur J Epidemiol
Gunst, Staerke, Pahus, Kristensen, Bodilsen et al., Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial, EClinicalMedicine
Harrison, Lin, Wang, Mechanisms of SARS-CoV-2 transmission and pathogenesis, Trends Immunol
Hashemzaei, Far, Yari, Heravi, Tabrizian et al., Anticancer and apoptosis-inducing effects of quercetin in vitro and in vivo, Oncol Rep
Hiremath, Kumar, Nandan, Mantesh, Shankarappa et al., In silico docking analysis revealed the potential of phytochemicals present in Phyllanthus amarus and Andrographis paniculata, used in Ayurveda medicine in inhibiting SARS-CoV-2, 3 Biotech
Horita, Fukumoto, Global case fatality rate from COVID-19 has decreased by 96.8% during 2.5 years of the pandemic, J Med Virol
Kandeil, Mostafa, Kutkat, Moatasim, Al-Karmalawy et al., Bioactive polyphenolic compounds showing strong antiviral activities against severe acute respiratory syndrome coronavirus 2, Pathogens
Konwar, Maurya, Bose, A meta-analysis of safety of different regimens of remdesivir in COVID-19 patients, Curr Drug Saf
Liu, Raghuvanshi, Ceylan, Bolling, Quercetin and its metabolites inhibit recombinant human angiotensin-converting enzyme 2 (ACE2) activity, J Agric Food Chem
Manjunathan, Periyaswami, Rosita, Pandya, Selvaraj et al., Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein, BMC Bioinform
Marzi, Vakil, Bahmanyar, Zarenezhad, Paxlovid: mechanism of action, synthesis, and in silico study, BioMed Res Int
Msemburi, Karlinsky, Knutson, Aleshin-Guendel, Chatterji et al., The WHO estimates of excess mortality associated with the COVID-19 pandemic, Nature
Munafo, Donati, Brindani, Ottonello, Armirotti et al., Quercetin and luteolin are single-digit micromolar inhibitors of the SARS-CoV-2 RNAdependent RNA polymerase, Sci Rep
Najjar-Debbiny, Gronich, Weber, Khoury, Amar et al., Effectiveness of paxlovid in reducing severe coronavirus disease 2019 and mortality in high-risk patients, Clin Infect Dis
Ning, Wang, Wu, Chen, Pei et al., The COVID-19 vaccination and vaccine inequity worldwide: an empirical study based on global data, Int J Environ Res Public Health
Onishi, Mori, Kanbara, Habe, Ota et al., Green tea catechins adsorbed on the murine pharyngeal mucosa reduce influenza a virus infection, J Funct Foods
Pan, Fang, Zhang, Pan, Liu et al., Chinese herbal compounds against SARS-CoV-2: Puerarin and quercetin impair the binding of viral S-protein to ACE2 receptor, Comput Struct Biotechnol J
Pandey, Rai, Tahir, Wahab, Bandyopadhyay et al., Prevalence of comorbidities and symptoms stratified by severity of illness amongst adult patients with COVID-19: a systematic review, Arch Med Sci Atheroscler Dis
Paulke, Eckert, Schubert-Zsilavecz, Wurglics, Isoquercitrin provides better bioavailability than quercetin: comparison of quercetin metabolites in body tissue and brain sections after six days administration of isoquercitrin and quercetin, Pharmazie
Schaefer, Jung, Hummer, Binding of SARS-CoV-2 fusion peptide to host endosome and plasma membrane, J Phys Chem B
Singh, Barry, Croatt, Ackerman, Grande et al., The spike protein of SARS-CoV-2 induces heme oxygenase-1: pathophysiologic implications, Biochim Biophys Acta -Mol Basis Dis
Sun, Sui, Zhou, Ya, Yuan et al., Structural basis of covalent inhibitory mechanism of TMPRSS2-related serine proteases by camostat, J Virol
Tsuchiya, Membrane interactions of phytochemicals as their molecular mechanism applicable to the discovery of drug leads from plants, Molecules
Tsuchiya, Structure-dependent membrane interaction of flavonoids associated with their bioactivity, Food Chem
Yang, Wang, Long, Li, Its main pharmacological activity and potential application in clinical medicine, Oxid Med Cell Longev
Yuan, Pavel, Wang, Kwachukwu, Mediouni et al., Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture, Commun Biol
Zhang, Hao, Zhang, He, Chen et al., Potential of green tea EGCG in neutralizing SARS-CoV-2 Omicron variant with greater tropism toward the upper respiratory tract, Trends Food Sci Technol
Zhu, Declercq, Creemers, Chen, Cui et al., Limitations of inhibitory activities of polyphenols on furin-mediated substrate processing, Curr Med Chem
Zhu, Scholle, Kisthardt, Xie, Flavonols and dihydroflavonols inhibit the main protease activity of SARS-CoV-2 and the replication of human coronavirus 229, E. Virology
Zhu, Van De Ven, Verbiest, Koeckelberghs, Chen et al., Polyphenols can inhibit furin in vitro as a result of the reactivity of their auto-oxidation products to proteins, Curr Med Chem
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