Targeting CoV-2 Spike RBD: ACE-II complex with phenolic compounds from Cistus (Cistus L.) Bee Pollen for COVID-19 treatment by Molecular Docking Study

Yıl 2020, , 10 - 23, 06.10.2020

Halil İbrahim Güler , Yakup Kara

https://doi.org/10.35206/jan.762734

Cited By: 5

Öz

Spike glycoprotein on the surface of the SARS-CoV-2 is a class I fusion protein that plays a role in the initial attachment of the virus to the human ACE-II receptor. ACE-II has been implicated in the regulation of heart function and also as a functional receptor for the coronavirus that causes the severe acute respiratory syndrome (SARS). In the present study, a molecular docking study was performed using eleven flavonoids present in Cistus bee pollen against the CoV-2 Spike RBD/ACE-II complex and compared their affinity with the FDA approved drug hydroxychloroquine (HCQ).
Binding constants of eleven flavonoids, catechin, pinocembrin, chrysin, caffeic acid phenethyl ester, p-OH Benzoic acid, syringic acid, t-cinnamic acid, p-Coumaric acid, rutin, ferulic acid and gallic acid were measured using the AutoDock 4.2 molecular docking software. Also, these binding constants were then compared to the reference molecule of hydroxychloroquine.
According to docking analysis, the results showed us that catechin has the best inhibiton potential among the all analyzed molecules with the high binding energy (-7.77 kcal/mol) and the lowest Ki (2.03 µM) and it is followed by pinocembrin, chrysin, caffeic acid phenethyl ester, respectively. Besides, the reference molecule hydroxychloroquine has binding energy of -7.53 kcal/mol and 3.04 µM. Consequently, high potential of flavonoids in extracts of Cistus bee pollen to interact with CoV-2 Spike RBD/ACE-II complex indicates that this natural product has high potential for Covid-19 treatment, but this needs to be supported by further studies

Anahtar Kelimeler

Covid-19, Cistus (Cistus L.) Bee Pollen, flavonoids, ,CoV-2 Spike RBD/ACE-II, molecular docking

Kaynakça

• Chan, J. F., Kok, K., Zhu, Z., Chu, H., To, K. K., Yuan, S., Yuen, K. (2020). Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerging Microbes & Infections, 9(1), 221-236. DOI: 10.1080/22221751.2020.1719902
• Chen, D., Oezguen, N., Urvil, P., Ferguson, C., Dann, S. M., Savidge, T. C. (2016) Regulation of protein-ligand binding affinity by hydrogen bond pairing. Science advances, 2(3), e1501240.
• Chen, H. & Du, Q. (2020). Potential natural compounds for preventing 2019-nCoV infection. Preprints,: 202001.0358.v1.
• Dassault Systèmes BIOVIA, Discovery Studio Modeling Environment, Release 2017, San Diego: Dassault Systèmes, 2016.
• Fehr, A. R., Perlman, S. (2015). Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol., 2015, 1282:1-23.
• Hughes, J. P., Rees, S., Kalindjian, S. B., Philpott, K. L. (2011). Principles of early drug discovery. British journal of pharmacology, 162(6), 1239-1249.
• Human, H., Nicolson, S. W. (2006). Nutritional content of fresh, bee-collected and stored pollen of Aloe greatheadii var. davyana (Asphodelaceae). Phytochemistry, 67, 1486-1492;
• Ikeno K, Kakimoto K, Nakamura T, Ikeno T, Shinohara R. (2004), Antioxidative activity of honeybee pollen: Comparison with other bee products. Honeybee Science-Tamagawa University (Japan);
• Joshipura, K.J, Hu, F.B., Manson, J.E., Stampfer, M.J., Rimm, E., Frank, E., Colditz, G., Ascherio, A., Rosner, B., Spiegelman, D. and Willett, W. (2001) The effect of fruit and vegetable intake on risk for coronary heart disease. Ann Intern Med., 134, 1106–1114.
• Kirchdoerfer RN, Cottrell CA, Wang N, Pallesen J, Yassine HM, Turner HL, Corbett KS, Graham BS, McLellan JS, Ward AB: Pre-fusion structure of a human coronavirus spike protein. Nature 2016, 531(7592):118-121.
• Koç AN, Silici S, Kasap F, Hörmet-Öz HT, Mavus-Buldu H, Ercal BD. (2011) Antifungal activity of the honeybee products against Candida spp. and Trichosporon spp. Journal of Medicinal Food, 14, 128-134.
• Kocot J, Kiełczykowska M, Luchowska-Kocot D, Kurzepa J, Musik I. (2018). Antioxidant Potential of Propolis, Bee Pollen, and Royal Jelly: Possible Medical Application. Oxid Med Cell Longev. May 2;2018:7074209.
• Komosinska-Vassev K, Olczyk P, Kaźmierczak J, Mencner L, Olczyk K. (2015) Bee pollen: chemical composition and therapeutic application. Evidence-Based Complementary and Alternative Medicine, 2015, Article ID 297425
• Kris-Etherton, P., Keen, C. (2002) Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Curr Opin Lipidol., 13, 41–49.
• Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020;19(3):149-150. doi:10.1038/d41573-020-00016-0
• Li, F, Li, WH, Farzan, M, Harrison, SC. (2005). Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science, 309, 1864–1868.
• Maruyama, H., Sakamoto, T., Araki, Y., Hara, H. (2010). Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema. BMC Complementary and Alternative Medicine, 10, 30.
• 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. J Comput Chem., 30, 2785–2791.
• Muhammad, S. A. and Fatima, N. (2015). In silico analysis and molecular docking studies of potential angiotensin-converting enzyme inhibitor using quercetin glycosides. Pharmacognosy magazine, 11(Suppl 1), S123.
• Nikolaos, S., Christodoulakis, M. G., Costas F. (2014). Leaf Structure of Cistus creticus L. (Rock Rose), a Medicinal Plant Widely Used in Folk Remedies Since Ancient Times. Journal of Herbs, Spices & Medicinal Plants, 20(2), 103-11.
• Papaefthimiou, D., Papanikolaou, A., Falara, V., Givanoudi, S., Kostas, S., and Kanellis, A. K. (2014). Genus Cistus: a model for exploring labdane-type diterpenes' biosynthesis and a natural source of high value products with biological, aromatic, and pharmacological properties. Frontiers in chemistry, 2, 35.
• Raj, S., Sasidharan, S., Dubey, V. K., Saudagar, P. (2019). Identification of lead molecules against potential drug target protein MAPK4 from L. donovani: An in-silico approach using docking, molecular dynamics and binding free energy calculation. PloS one, 14(8), e0221331.
• Sargin, S. A., and Selvi, S. (2016). Türkiye’de Yayılış Gösteren Cistus L.(Cistaceae) Cinsinin Karşılaştırmalı Yaprak Anatomisi. Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 6(2), 41-48.
• Senathilake, K., Samarakoon, S. Tennekoon, K. (2020). Virtual Screening of Inhibitors Against Spike Glycoprotein of 2019 Novel Corona Virus: A Drug Repurposing Approach., DOI: 10.20944/preprints202003.0042.v1 (preprint)
• Senathilake, K. S., Samarakoon, S. R., Tennekoon, K.H. (2020). Virtual screening of inhibitors against spike glycoprotein of 2019 novel corona virus: a drug repurposing approach. Preprints. DOI: 10.20944/preprints202003.0042.v1
• Smith, M. and Smith, J. C. (2020). Repurposing therapeutics for COVID-19: supercomputer-based docking to the SARS-CoV-2 viral spike protein and viral spike protein-human ACE-II interface. ChemRxiv. DOI: 10.26434/chemrxiv.11871402.v3
• Ulusoy, E., and Kolayli, S. (2014). Phenolic composition and antioxidant properties of Anzer bee pollen. Journal of Food Biochemistry, 38(1), 73-82
• Wang, Y, Zhang, D, Du, G. et al. (2020). Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet, Apr 29. Doi: 10.1016/S0140-6736(20)31022-9.
• Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C., Abiona, O., Graham, B. S., McLellan, J. S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. DOI: 10.1126/science.abb2507
• Wu, K. L., Peng, G. Q., Wilken, M., Geraghty, R. J. and Li, F. (2012) Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus. J Biol Chem., 287, 8904–8911
• Xia, S., Zhu, Y., Liu, M., Lan, Q., Xu, W., Wu, Y., Ying, T., Liu, S., Shi, Z., Jiang, S., Lu, L. (2020). Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cellular & Molecular Immunology, DOI: 10.1038/s41423-020-0374-2
• Gorbalenya, A. E., Baker, S. C., Baric, R. S. et al. (2020). The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol., 5, 536–544. https://doi.org/10.1038/s41564-020-0695-z
• Yan, R., Zhang, Y., Li, Y., Xia, L., Guo, Y., Zhou, Q. (2020). Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE-II. Science. DOI: 10.1126/science.abb2762 Wang, J. (2020). Fast identification of possible drug treatment of coronavirus disease-19 (COVID-19) through computational drug repurposing study, ChemRxiv. DOI: 10.26434/chemrxiv.11875446.v1
• Zhou, B., Yang, L., Liu, Z.L. (2000). Antioxidative effects of green tea polyphenols on free radical initiated and photosensitized peroxidation of human low density lipoprotein. Chem Phys Lipids, 106: 53–63.