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Research Articles

In silico analysis of dietary polyphenols and their gut microbial metabolites suggest inhibition of SARS-CoV-2 infection, replication, and host inflammatory mediators

ORCID Icon, , & ORCID Icon
Pages 14339-14357 | Received 09 Aug 2022, Accepted 09 Feb 2023, Published online: 20 Feb 2023

References

  • Agresti, N., Lalezari, J. P., Amodeo, P. P., Mody, K., Mosher, S. F., Seethamraju, H., Kelly, S. A., Pourhassan, N. Z., Sudduth, C. D., Bovinet, C., ElSharkawi, A. E., Patterson, B. K., Stephen, R., Sacha, J. B., Wu, H. L., Gross, S. A., & Dhody, K. (2021). Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: Case series of four critically ill patients treated with leronlimab. Journal of Translational Autoimmunity, 4, 100083. https://doi.org/10.1016/j.jtauto.2021.100083
  • Agus, A., Denizot, J., Thévenot, J., Martinez-Medina, M., Massier, S., Sauvanet, P., Bernalier-Donadille, A., Denis, S., Hofman, P., Bonnet, R., Billard, E., & Barnich, N. (2016). Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation. Scientific reports, 6(1), 1–14. https://doi.org/10.1038/srep19032
  • Al Kassaa, I., El Omari, S., Abbas, N., Papon, N., Drider, D., Kassem, I. I., & Osman, M. (2021). High association of COVID-19 severity with poor gut health score in Lebanese patients. PloS One, 16(10), e0258913. https://doi.org/10.1371/journal.pone.0258913
  • Anand, K., Ziebuhr, J., Wadhwani, P., Mesters, J. R., Hilgenfeld R. (2003). Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs. Science, 1763(5626), 1763–1768.
  • Anhê, F. F., Roy, D., Pilon, G., Dudonné, S., Matamoros, S., Varin, T. V., Garofalo, C., Moine, Q., Desjardins, Y., Levy, E., & Marette, A. (2015). A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut, 64(6), 872–883. https://doi.org/10.1136/gutjnl-2014-307142
  • Ayerbe, L., Risco, C., & Ayis, S. (2020). The association between treatment with heparin and survival in patients with Covid-19. Journal of Thrombosis and Thrombolysis, 50(2), 298–301. https://doi.org/10.1007/s11239-020-02162-z
  • Báez-Santos, Y. M., John, S. E. S., & Mesecar, A. D. (2015). The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds. Antiviral Research, 115(January), 21–38. https://doi.org/10.1016/j.antiviral.2014.12.015
  • Basha, G. M., Parulekar, R. S., Al-Sehemi, A. G., Pannipara, M., Siddaiah, V., Kumari, S., Choudhari., P. B., & Tamboli, Y. (2021). Design and in silico investigation of novel Maraviroc analogues as dual inhibition of CCR-5/SARS-CoV-2 M(pro). Journal of Biomolecular Structure & Dynamics, 40(21), 11095–11110.
  • Beck, M. A., Handy, J., & Levander, O. A. (2000). The role of oxidative stress in viral infections. Annals of the New York Academy of Sciences, 917, 906–912. https://doi.org/10.1111/j.1749-6632.2000.tb05456.x
  • Berman, H. M., Westbrook, J., & Feng, Z. (2000). The protein data bank. Nucleic Acids Research, 28(1), 235–242. https://doi.org/10.1093/nar/28.1.235
  • Calder, P., Carr, A., Gombart, A., & Eggersdorfer, M. (2020). Optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections. Nutrients, 12(4), 1181–1181. https://doi.org/10.3390/nu12041181
  • Carmody, R. N., Gerber, G. K., Luevano, J. M., Gatti, D. M., Somes, L., Svenson, K. L., & Turnbaugh, P. J. (2015). Diet dominates host genotype in shaping the murine gut microbiota. Cell Host & Microbe, 17(1), 72–84. https://doi.org/10.1016/j.chom.2014.11.010
  • Carvelli, J., Demaria, O., Vély, F., Batista, L., Chouaki Benmansour, N., Fares, J., Carpentier, S., Thibult, M.-L., Morel, A., Remark, R., André, P., Represa, A., Piperoglou, C., Assante Miranda, L., Baron, W., Belaid, N., Caillet, C., Caraguel, F., Carrette, B., … Vivier, E, the Explore COVID-19 IPH group. (2020). Association of COVID-19 inflammation with activation of the C5a–C5aR1 axis. Nature, 588(7836), 146–150. https://doi.org/10.1038/s41586-020-2600-6
  • Chen, P. Z., Bobrovitz, N., Premji, Z., Koopmans, M., Fisman, D. N., & Gu, F. X. (2021). Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets and aerosols. eLife, 10, e65774. https://doi.org/10.7554/eLife.65774
  • Choy, Y. Y., Jaggers, G. K., Oteiza, P. I., & Waterhouse, A. L. (2013). Bioavailability of intact proanthocyanidins in the rat colon after ingestion of grape seed extract. Journal of Agricultural and Food Chemistry, 61(1), 121–127. https://doi.org/10.1021/jf301939e
  • Coperchini, F., Chiovato, L., Croce, L., Magri, F., & Rotondi, M. (2020). The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine & Growth Factor Reviews, 53, 25–32. https://doi.org/10.1016/j.cytogfr.2020.05.003
  • Dashraath, P., Wong, J. L. J., Lim, M. X. K., Lim, L. M., Li, S., Biswas, A., Choolani, M., Mattar, C., & Su, L. L, (2020). Coronavirus disease 2019 (COVID-19) pandemic and pregnancy. American Journal of Obstetrics and Gynecology, 222(6), 521–531. https://doi.org/10.1016/j.ajog.2020.03.021
  • Del Bo’, C., Bernardi, S., Marino, M., Porrini, M., Tucci, M., Guglielmetti, S., Cherubini, A., Carrieri, B., Kirkup, B., Kroon, P., Zamora-Ros, R., Hidalgo Liberona, N., Andres-Lacueva, C., & Riso, P. (2019). Systematic review on polyphenol intake and health outcomes: Is there sufficient evidence to define a health-promoting polyphenol-rich dietary pattern? Nutrients, 11(6), 1355–1355., https://doi.org/10.3390/nu11061355
  • Ejaz, H., Alsrhani, A., Zafar, A., Javed, H., Junaid, K., Abdalla, A. E., Abosalif, K. O., Ahmed, Z., & Younas, S. (2020). COVID-19 and comorbidities: Deleterious impact on infected patients. Journal of Infection and Public Health, 13(12), 1833–1839. https://doi.org/10.1016/j.jiph.2020.07.014
  • Enaud, R., Prevel, R., Ciarlo, E., Beaufils, F., Wieërs, G., Guery, B., & Delhaes, L. (2020). The gut-lung axis in health and respiratory diseases: A place for inter-organ and inter-kingdom crosstalks. Frontiers in Cellular and Infection Microbiology, 10, 9–9. https://doi.org/10.3389/fcimb.2020.00009
  • Everard, A., Belzer, C., Geurts, L., Ouwerkerk, J. P., Druart, C., Bindels, L. B., Guiot, Y., Derrien, M., Muccioli, G. G., Delzenne, N. M., de Vos, W. M., & Cani, P. D. (2013). Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proceedings of the National Academy of Sciences, 110(22), 9066–9071. https://doi.org/10.1073/pnas.1219451110
  • Ferreira, J. C., Fadl, S., Villanueva, A. J., & Rabeh, W. M. (2021). Catalytic dyad residues His41 and Cys145 impact the catalytic activity and overall conformational fold of the main SARS-CoV-2 protease 3-chymotrypsin-like protease. Frontiers in Chemistry, 9, 692168. https://doi.org/10.3389/fchem.2021.692168
  • Gao, X., Qin, B., Chen, P., Zhu, K., Hou, P., Wojdyla, J. A., Wang, M., & Cui, S. (2021). Crystal structure of SARS-CoV-2 papain-like protease. Acta Pharmaceutica Sinica B, 11(1), 237–245. https://doi.org/10.1016/j.apsb.2020.08.014
  • Gu, S., Chen, Y., Wu, Z., Chen, Y., Gao, H., Lv, L., Guo, F., Zhang, X., Luo, R., Huang, C., Lu, H., Zheng, B., Zhang, J., Yan, R., Zhang, H., Jiang, H., Xu, Q., Guo, J., Gong, Y., Tang, L., & Li, L. (2020). Alterations of the gut microbiota in patients with coronavirus disease 2019 or H1N1 influenza. Clinical Infectious Diseases, 71(10), 2669–2678. https://doi.org/10.1093/cid/ciaa709
  • Hamming, I., Timens, W., Bulthuis, M. L. C., Lely, A. T., Navis, G. J., & van Goor, H. (2004). Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. The Journal of Pathology, 203(2), 631–637. https://doi.org/10.1002/path.1570
  • Han, P., Li, L., Liu, S., Wang, Q., Zhang, D., Xu, Z., Han, P., Li, X., Peng, Q., Su, C., Huang, B., Li, D., Zhang, R., Tian, M., Fu, L., Gao, Y., Zhao, X., Liu, K., Qi, J., Gao, G. F., & Wang, P. (2022). Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2. Cell, 185(4), 630–640.e10. https://doi.org/10.1016/j.cell.2022.01.001
  • Hanwell, M. D., Curtis, D. E., Lonie, D. C., Vandermeersch, T., Zurek, E., & Hutchison, G. R. (2012). Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. Journal of Cheminformatics, 4(1), 17–17. https://doi.org/10.1186/1758-2946-4-17
  • He, J., Magnuson, B. A., & Giusti, M. M. (2005). Analysis of anthocyanins in rat intestinal contents—Impact of anthocyanin chemical structure on fecal excretion. Journal of Agricultural and Food Chemistry, 53(8), 2859–2866. https://doi.org/10.1021/jf0479923
  • Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 181(2), 271–280.e8. https://doi.org/10.1016/j.cell.2020.02.052
  • Hussain, I., Cher, G. L. Y., Abid, M. A., & Abid, M. B. (2021). Role of gut microbiome in COVID-19: An insight into pathogenesis and therapeutic potential. Frontiers in Immunology, 12, 765965. https://doi.org/10.3389/fimmu.2021.765965
  • Jakubik, J., Randakova, A., & Dolezal, V. (2013). On homology modeling of the M(2) muscarinic acetylcholine receptor subtype. Journal of Computer-Aided Molecular Design, 27(6), 525–538. https://doi.org/10.1007/s10822-013-9660-8
  • Kaihatsu, K., Yamabe, M., & Ebara, Y. (2018). Antiviral mechanism of action of epigallocatechin-3-O-gallate and its fatty acid esters. Molecules, 23(10), 2475. https://doi.org/10.3390/molecules23102475
  • Kardum, N., & Glibetic, M. (2018). Chapter three—Polyphenols and their interactions with other dietary compounds: Implications for human health. In F. Toldrá (Ed.) Advances in Food and Nutrition Research (Vol. 84, pp. 103–144). Academic Press.
  • Kim, H. S. (2021). Do an altered gut microbiota and an associated leaky gut affect COVID-19 severity? mBio, 12(1), e03022-20. https://doi.org/10.1128/mBio.03022-20
  • Kim, S. Y., Jin, W., Sood, A., Montgomery, D. W., Grant, O. C., Fuster, M. M., Fu, L., Dordick, J. S., Woods, R. J., Zhang, F., & Linhardt, R. J. (2020). Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions. Antiviral Research, 181, 104873. https://doi.org/10.1016/j.antiviral.2020.104873
  • Kim, S. H., Kim, J., Jang, J. Y., Noh, H., Park, J., Jeong, H., Jeon, D., Uhm, C., Oh, H., Cho, K., Jeon, Y., On, D., Yoon, S., Lim, S.-Y., Kim, S. P., Lee, Y. W., Jang, H. J., Park, I. H., Oh, J., … Seong, J. K. (2022). Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits. Frontiers in Immunology. 13, 1055811.
  • Kim, H., Rebholz, C. M., Hegde, S., LaFiura, C., Raghavan, M., Lloyd, J. F., Cheng, S., & Seidelmann, S. B. (2021). Plant-based diets, pescatarian diets and COVID-19 severity: A population-based case–control study in six countries. BMJ Nutrition, Prevention & Health, 4(1), 257–266. https://doi.org/10.1136/bmjnph-2021-000272
  • Kneller, D. W., Phillips, G., O’Neill, H. M., Jedrzejczak, R., Stols, L., Langan, P., Joachimiak, A., Coates, L., & Kovalevsky, A. (2020). Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography. Nature Communications, 11(1), 7–12. https://doi.org/10.1038/s41467-020-16954-7
  • Krieger, E., & Vriend, G. (2015). New ways to boost molecular dynamics simulations. Journal of Computational Chemistry, 36(13), 996–1007. https://doi.org/10.1002/jcc.23899
  • Kuhn, P., Kalariya, H. M., Poulev, A., Ribnicky, D. M., Jaja-Chimedza, A., Roopchand, D. E., & Raskin, I. (2018). Grape polyphenols reduce gut-localized reactive oxygen species associated with the development of metabolic syndrome in mice. PLos One, 13(10), e0198716.
  • Kumar, R., Murugan, N. A., & Srivastava, V. (2022). Improved binding affinity of omicron’s spike protein for the human angiotensin-converting enzyme 2 receptor is the key behind its increased virulence. International Journal of Molecular Sciences, 23(6), 3409–3411. https://doi.org/10.3390/ijms23063409
  • Kurtz, A., Grant, K., Marano, R., Arrieta, A., Grant, K., Feaster, W., Steele, C., & Ehwerhemuepha, L. (2021). Long-term effects of malnutrition on severity of COVID-19. Scientific Reports, 11(1), 1–8. https://doi.org/10.1038/s41598-021-94138-z
  • Lan, J., Ge, J., Yu, J., Shan, S., Zhou, H., Fan, S., Zhang, Q., Shi, X., Wang, Q., Zhang, L., & Wang, X. (2020). Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, 581(7807), 215–220. https://doi.org/10.1038/s41586-020-2180-5
  • Lee, T., Kwon, H.-S., Bang, B.-R., Lee, Y. S., Park, M.-Y., Moon, K.-A., Kim, T.-B., Lee, K.-Y., Moon, H.-B., & Cho, Y. S. (2012). Grape seed proanthocyanidin extract attenuates allergic inflammation in murine models of asthma. Journal of Clinical Immunology, 32(6), 1292–1304. https://doi.org/10.1007/s10875-012-9742-8
  • Liao, Y., Li, X., Mou, T., Zhou, X., Li, D., Wang, L., Zhang, Y., Dong, X., Zheng, H., Guo, L., Liang, Y., Jiang, G., Fan, S., Xu, X., Xie, Z., Chen, H., Liu, L., & Qihan, L. (2020). Distinct infection process of SARS-CoV-2 in human bronchial epithelial cells line. Journal of Medical Virology, 92(11), 2830-2838. https://doi.org/10.1002/jmv.26200-10.1002/jmv.26200
  • Liu, H., Kim, H. R., Deepak, R. N. V. K., Wang, L., Chung, K. Y., Fan, H., Wei, Z., & Zhang, C. (2018). Orthosteric and allosteric action of the C5a receptor antagonists. Nature Structural & Molecular Biology, 25(6), 472–481. https://doi.org/10.1038/s41594-018-0067-z
  • Losso, J. N., Losso, M. N., Toc, M., Inungu, J. N., & Finley, J. W. (2021). The young age and plant-based diet hypothesis for low SARS-CoV-2 infection and COVID-19 pandemic in Sub-Saharan Africa. Plant Foods for Human Nutrition, 76(3), 270–280. https://doi.org/10.1007/s11130-021-00907-6
  • Ma, C., Sacco, M. D., Hurst, B., Townsend, J. A., Hu, Y., Szeto, T., Zhang, X., Tarbet, B., Marty, M. T., Chen, Y., & Wang, J. (2020). Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Research, 30(8), 678–692. https://doi.org/10.1038/s41422-020-0356-z
  • Maier, J., Martinez, C., Kasavajhala, K., et al. (2015). ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB. Journal of Chemical Theory and Computation, 176(1), 100–106.
  • Manach, C., Scalbert, A., Morand, C., Rémésy, C., & Jiménez, L. (2004). Polyphenols: Food sources and bioavailability. The American Journal of Clinical Nutrition, 79(5), 727–747. https://doi.org/10.1093/ajcn/79.5.727
  • Manach, C., Williamson, G., Morand, C., Scalbert, A., & Rémésy, C. (2005). Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. The American Journal of Clinical Nutrition, 81(1 Suppl), 230S–242S. https://doi.org/10.1093/ajcn/81.1.230S
  • Mannar, D., Saville, J. W., Zhu, X., Srivastava, S. S., Berezuk, A. M., Tuttle, K. S., Marquez, A. C., Sekirov, I., & Subramaniam, S. (2022). SARS-CoV-2 omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex. Science, 375(6582), 760–764. https://doi.org/10.1126/science.abn7760
  • Mastellos, D. C., Yancopoulou, D., Kokkinos, P., Huber-Lang, M., Hajishengallis, G., Biglarnia, A. R., Lupu, F., Nilsson, B., Risitano, A. M., Ricklin, D., & Lambris, J. D. (2015). Compstatin: A C3-targeted complement inhibitor reaching its prime for bedside intervention. European Journal of Clinical Investigation, 45(4), 423–440. https://doi.org/10.1111/eci.12419
  • Meng, X., Lee, M.-J., Li, C., et al. (2001). Formation and identification of 4′-O-methyl-(−)-epigallocatechin in humans. Drug Metabolism and Disposition, 29(6), 789–793.
  • Merino, J., Joshi, A. D., Nguyen, L. H., Leeming, E. R., Mazidi, M., Drew, D. A., Gibson, R., Graham, M. S., Lo, C.-H., Capdevila, J., Murray, B., Hu, C., Selvachandran, S., Hammers, A., Bhupathiraju, S. N., Sharma, S. V., Sudre, C., Astley, C. M., Chavarro, J. E., … Chan, A. T. (2021). Diet quality and risk and severity of COVID-19: A prospective cohort study. Gut, 70(11), 2096–2104. https://doi.org/10.1136/gutjnl-2021-325353
  • Merle, N. S., Noe, R., Halbwachs-Mecarelli, L., Fremeaux-Bacchi, V., & Roumenina, L. T. (2015). Complement system part II: Role in immunity. Frontiers in Immunology, 6, 257–257. https://doi.org/10.3389/fimmu.2015.00257
  • Mezhibovsky, E., Knowles, K. A., He, Q., Sui, K., Tveter, K. M., Duran, R. M., Roopchand, D. E. (2021). Grape polyphenols attenuate diet-induced obesity and hepatic steatosis in mice in association with reduced butyrate and increased markers of intestinal carbohydrate oxidation. Frontiers in Nutrition, 8, 675267.
  • Mobley, D. L., & Dill, K. A. (2009). Apr 15 2009 Binding of small-molecule ligands to proteins: "What you see" is not always "what you get" [Research Article. ]. Structure, 17(4), 489–498. https://doi.org/10.1016/j.str.2009.02.010
  • Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785–2791. https://doi.org/10.1002/jcc.21256
  • Moustaqil, M., Ollivier, E., Chiu, H.-P., Van Tol, S., Rudolffi-Soto, P., Stevens, C., Bhumkar, A., Hunter, D. J. B., Freiberg, A. N., Jacques, D., Lee, B., Sierecki, E., & Gambin, Y. (2021). SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): Implications for disease presentation across species. Emerging Microbes & Infections, 10(1), 178–195. https://doi.org/10.1080/22221751.2020.1870414
  • Osipiuk, J., Azizi, S.-A., Dvorkin, S., Endres, M., Jedrzejczak, R., Jones, K. A., Kang, S., Kathayat, R. S., Kim, Y., Lisnyak, V. G., Maki, S. L., Nicolaescu, V., Taylor, C. A., Tesar, C., Zhang, Y.-A., Zhou, Z., Randall, G., Michalska, K., Snyder, S. A., Dickinson, B. C., & Joachimiak, A. (2021). Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors. Nature Communications, 12(1), 1–9. https://doi.org/10.1038/s41467-021-21060-3
  • Ozdal, T., Sela, D. A., Xiao, J., Boyacioglu, D., Chen, F., & Capanoglu, E. (2016). The reciprocal interactions between polyphenols and gut microbiota and effects on bioaccessibility. Nutrients, 8(2), 78–36. https://doi.org/10.3390/nu8020078
  • Patel, S., Saxena, B., & Mehta, P. (2021). Recent updates in the clinical trials of therapeutic monoclonal antibodies targeting cytokine storm for the management of COVID-19. Heliyon, 7(2), e06158. https://doi.org/10.1016/j.heliyon.2021.e06158
  • Patterson, B. K., Seethamraju, H., Dhody, K., Corley, M. J., Kazempour, K., Lalezari, J., Pang, A. P., Sugai, C., Mahyari, E., Francisco, E. B., Pise, A., Rodrigues, H., Wu, H. L., Webb, G. M., Park, B. S., Kelly, S., Pourhassan, N., Lelic, A., Kdouh, L., … Sacha, J. B. (2021). CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14. International Journal of Infectious Diseases, 103, 25–32. https://doi.org/10.1016/j.ijid.2020.10.101
  • Rajpal, A., Rahimi, L., & Ismail-Beigi, F. (2020). Factors leading to high morbidity and mortality of COVID-19 in patients with type 2 diabetes. Journal of Diabetes, 12(12), 895-908. https://doi.org/10.1111/1753-0407.13085
  • Ratia, K., Kilianski, A., Baez-Santos, Y. M., Baker, S. C., & Mesecar, A. (2014). Structural basis for the ubiquitin-linkage specificity and deISGylating activity of SARS-CoV papain-like protease. PLoS Pathogens, 10(5), e1004113. https://doi.org/10.1371/journal.ppat.1004113
  • Ratia, K., Pegan, S., Takayama, J., Sleeman, K., Coughlin, M., Baliji, S., Chaudhuri, R., Fu, W., Prabhakar, B. S., Johnson, M. E., Baker, S. C., Ghosh, A. K., & Mesecar, A. D. (2008). A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication. Proceedings of the National Academy of Sciences, 105(42), 16119–16124. https://doi.org/10.1073/pnas.0805240105
  • Ribnicky, D. M., Roopchand, D. E., Oren, A., Grace, M., Poulev, A., Lila, M. A., Havenaar, R., & Raskin, I. (2014). Effects of a high fat meal matrix and protein complexation on the bioaccessibility of blueberry anthocyanins using the TNO gastrointestinal model (TIM-1). Food Chemistry, 142, 349–357.
  • Ribnicky, D. M., Roopchand, D. E., Poulev, A., Kuhn, P., Oren, A., Cefalu, W. T., & Raskin, I. (2014). Artemisia dracunculus L. polyphenols complexed to soy protein show enhanced bioavailability and hypoglycemic activity in C57BL/6 mice. Nutrition (Burbank, Los Angeles County, Calif.), 30(7-8 Suppl), S4–S10.
  • Rodríguez-Daza, M. C., Pulido-Mateos, E. C., Lupien-Meilleur, J., Guyonnet, D., Desjardins, Y., & Roy, D. (2021). Polyphenol-mediated gut microbiota modulation: Toward prebiotics and further. Frontiers in Nutrition, 8(June), 689456. https://doi.org/10.3389/fnut.2021.689456
  • Rohaim, M. A., El Naggar, R. F., Clayton, E., & Munir, M. (2021). Structural and functional insights into non-structural proteins of coronaviruses. Microbial Pathogenesis, 150, 104641–104641. https://doi.org/10.1016/j.micpath.2020.104641
  • Roopchand, D. E., Carmody, R. N., Kuhn, P., Moskal, K., Rojas-Silva, P., Turnbaugh, P. J., & Raskin, I. (2015). Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet—Induced metabolic syndrome. Diabetes, 64(8), 2847–2858. https://doi.org/10.2337/db14-1916
  • Roopchand, D. E., Kuhn, P., Krueger, C. G., Moskal, K., Lila, M. A., & Raskin, I. (2013). Concord grape pomace polyphenols complexed to soy protein isolate are stable and hypoglycemic in diabetic mice. Journal of Agricultural and Food Chemistry, 61(47), 11428–11433. https://doi.org/10.1021/jf403238e
  • Rottman, J. B., Ganley, K. P., Williams, K., Wu, L., Mackay, C. R., & Ringler, D. J. (1997). Cellular localization of the chemokine receptor CCR5. The American Journal of Pathology, 151(5), 1341–1351.
  • Sahoo, A. R., Mishra, R., & Rana, S. (2018). The model structures of the complement component 5a receptor (C5aR) bound to the native and engineered (h). Scientific Reports, 8(1), 2955–2955. https://doi.org/10.1038/s41598-018-21290-4
  • Schwarz, S., Sauter, D., Wang, K., Zhang, R., Sun, B., Karioti, A., Bilia, A. R., Efferth, T., & Schwarz, W. (2014). Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus. Planta Medica, 80(2-3), 177–182. https://doi.org/10.1055/s-0033-1360277
  • Serra, A., Macià, A., Rubió, L., Anglès, N., Ortega, N., Morelló, J. R., Romero, M.-P., & Motilva, M.-J. (2013). Distribution of procyanidins and their metabolites in rat plasma and tissues in relation to ingestion of procyanidin-enriched or procyanidin-rich cocoa creams. European Journal of Nutrition, 52(3), 1029–1038. https://doi.org/10.1007/s00394-012-0409-2
  • Shamsi, A., Mohammad, T., Anwar, S., AlAjmi, M. F., Hussain, A., Rehman, M. T., Islam, A., & Hassan, M. I. (2020). Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: Possible implication in COVID-19 therapy. Bioscience Reports, 40(6), BSR20201256. https://doi.org/10.1042/BSR20201256
  • Shin, D., Mukherjee, R., Grewe, D., Bojkova, D., Baek, K., Bhattacharya, A., Schulz, L., Widera, M., Mehdipour, A. R., Tascher, G., Geurink, P. P., Wilhelm, A., van der Heden van Noort, G. J., Ovaa, H., Müller, S., Knobeloch, K.-P., Rajalingam, K., Schulman, B. A., Cinatl, J., … Dikic, I. (2020). Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature, 587(7835), 657–662. https://doi.org/10.1038/s41586-020-2601-5
  • Sholzberg, M., da Costa, B. R., Tang, G. H., Rahhal, H., AlHamzah, M., Baumann Kreuziger, L., Ní Áinle, F., Almarshoodi, M. O., James, P. D., Lillicrap, D., Carrier, M., Beckett, A., Fralick, M., Middeldorp, S., Lee, A. Y., Thorpe, K. E., Negri, E. M., Cushman, M., & Jüni, P. (2021). Randomized trials of therapeutic heparin for COVID-19: A meta-analysis. Research and Practice in Thrombosis and Haemostasis, 5(8), e12638. https://doi.org/10.1002/rth2.12638
  • Smith, T. J., & McClung, J. P. (2021). Nutrition, immune function, and infectious disease. Medical Journal (Fort Sam Houston, Tex), 133–136. (PB 8-21-01/02/03). PMID: 33666926.
  • Sonnenburg, E. D., Smits, S. A., Tikhonov, M., Higginbottom, S. K., Wingreen, N. S., & Sonnenburg, J. L. (2016). Diet-induced extinction in the gut microbiota compounds over generations. Nature, 529(7585), 212–215. https://doi.org/10.1038/nature16504
  • Suardi, C., Cazzaniga, E., Graci, S., Dongo, D., & Palestini, P. (2021). Link between viral infections, immune system, inflammation and diet. International Journal of Environmental Research and Public Health, 18(5), 2455–2413. https://doi.org/10.3390/ijerph18052455
  • Tatsi, E.-B., Filippatos, F., & Michos, A. (2021). SARS-CoV-2 variants and effectiveness of vaccines: A review of current evidence. Epidemiology and Infection, 149, e237. https://doi.org/10.1017/S0950268821002430
  • Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461.
  • Wu, W., Li, R., Li, X., He, J., Jiang, S., Liu, S., & Yang, J. (2015). Quercetin as an antiviral agent inhibits influenza a virus (IAV) Entry. Viruses, 8(1), 6. https://doi.org/10.3390/v8010006
  • Xu, J., Chu, M., Zhong, F., Tan, X., Tang, G., Mai, J., Lai, N., Guan, C., Liang, Y., & Liao, G. (2020). Digestive symptoms of COVID-19 and expression of ACE2 in digestive tract organs. Cell Death Discovery, 6(1), 76–76. https://doi.org/10.1038/s41420-020-00307-w
  • Xu, J., Xu, Z., & Zheng, W. (2017). A review of the antiviral role of green tea catechins. Molecules, 22(8), 1337–1318. https://doi.org/10.3390/molecules22081337
  • Yahfoufi, N., Alsadi, N., Jambi, M., & Matar, C. (2018). The immunomodulatory and anti-inflammatory role of polyphenols. Nutrients, 10(11), 1618. https://doi.org/10.3390/nu10111618
  • Yeoh, Y. K., Zuo, T., Lui, G. C.-Y., Zhang, F., Liu, Q., Li, A. Y., Chung, A. C., Cheung, C. P., Tso, E. Y., Fung, K. S., Chan, V., Ling, L., Joynt, G., Hui, D. S.-C., Chow, K. M., Ng, S. S. S., Li, T. C.-M., Ng, R. W., Yip, T. C., … Ng, S. C. (2021). Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut, 70(4), 698–706. https://doi.org/10.1136/gutjnl-2020-323020
  • Yi, C., Sun, X., Ye, J., Ding, L., Liu, M., Yang, Z., Lu, X., Zhang, Y., Ma, L., Gu, W., Qu, A., Xu, J., Shi, Z., Ling, Z., & Sun, B. (2020). Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cellular & Molecular Immunology, 17(6), 621–630. https://doi.org/10.1038/s41423-020-0458-z
  • Zamora-Ros, R., Rabassa, M., Cherubini, A., Urpí-Sardà, M., Bandinelli, S., Ferrucci, L., & Andres-Lacueva, C. (2013). High concentrations of a urinary biomarker of polyphenol intake are associated with decreased mortality in older adults. The Journal of Nutrition, 143(9), 1445–1450. https://doi.org/10.3945/jn.113.177121
  • Zhang, H., Chen, K., Tan, Q., Shao, Q., Han, S., Zhang, C., Yi, C., Chu, X., Zhu, Y., Xu, Y., Zhao, Q., & Wu, B. (2021). Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5. Nature Communications, 12(1), 4151–4151. https://doi.org/10.1038/s41467-021-24438-5
  • Zhang, H., Jiang, L., Guo, H., Sun, J., Liu, X., Liu, R., Ding, Q., & Ren, F. (2013). The inhibitory effect of milk on the absorption of dietary phenolic acids and the change in human plasma antioxidant capacity through a mechanism involving both milk proteins and fats. Molecular Nutrition & Food Research, 57(7), 1228–1236.
  • Zheng, Y., Han, G. W., Abagyan, R., Wu, B., Stevens, R. C., Cherezov, V., Kufareva, I., & Handel, T. M. (2017). Structure of CC chemokine receptor 5 with a potent chemokine antagonist reveals mechanisms of chemokine recognition and molecular mimicry by HIV. Immunity, 46(6), 1005–1017.e5. https://doi.org/10.1016/j.immuni.2017.05.002
  • Zhou, D. Y., Fang, S. R., Zou, C. F., et al. (2015). Proanthocyanidin from grape seed extract inhibits airway inflammation and remodeling in a murine model of chronic asthma. Natural Products Communications. 10(2), 257–262.
  • Zuo, T., Zhang, F., Lui, G. C., Yeoh, Y. K., Li, A. Y., Zhan, H., Wan, Y., Chung, A. C., Cheung, C. P., Chen, N., Lai, C. K., Chen, Z., Tso, E. Y., Fung, K. S., Chan, V., Ling, L., Joynt, G., Hui, D. S., Chan, F. K., Chan, P. K., & Ng, S. C. (2020). Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology, 159(3), 944–955.e8. e8. https://doi.org/10.1053/j.gastro.2020.05.048

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