A perspective on natural potential compounds against SARS COV-2: The case of Bioflavonoids against 3C-like proteinase (3Cl-pro) and the role of Benzylisoquinoline Alkaloids, (BIAs), against SARS-CoV-2 Spike

I.V. Ferrari¹ , M. Di Mario² , R. Narducci³ , A. Bracco⁴ , P. Patrizio⁵

Section:Research Paper, Product Type: Journal-Paper
Vol.9 , Issue.6 , pp.35-40, Dec-2021

Online published on Dec 31, 2021

Copyright © I.V. Ferrari, M. Di Mario, R. Narducci, A. Bracco, P. Patrizio . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
 

View this paper at   Google Scholar | DPI Digital Library

XML View     PDF Download

How to Cite this Paper

Abstract :
In this paper, we have investigated two different typology natural compounds, by rapid molecular docking approach, using Autodock Vina with Pyrx Software. The main idea was focused to evaluated different bioflavonoids, against SARS COV-2 3C-like proteinase, (3Cl-pro). From our results of Molecular Docking, in the Ligand Binding Site pocket, we have proposed six active flavonoids, equipped with high Binding Energy Score (kcal/mol), about -10 kcal/mol-1. They are Sequoiaflavone, Bilobetin, Cupressuflavone, Amentoflavone, Ginkgetin, and Theaflavin, respectively, potentially useful against 3Cl-pro. Moreover, we have also performed another category, equipped with anticancer properties. They are Benzylisoquinoline Alkaloids ( BIAs), in which they are potentially active against SPIKE-SARS-CoV-2 RBD, demonstrating that BIAs exhibited significantly higher binding Energy values of ca -10; -11 kcal mol-1, in the Receptor Binding Domain of Spike Glycoprotein.

Key-Words / Index Term :
Docking; Benzylisoquinoline Alkaloids; Bioflavonoids

References :
[1] Hu, B., Guo, H., Zhou, P., & Shi, Z. L.” Characteristics of SARS-CoV-2 and COVID-19”, Nature reviews. Microbiology, Vol. 19, Issue.3, pp.141–154. 2021. https://doi.org/10.1038/s41579-020-00459-7.
[2] Hatmal, M. M., Alshaer, W., Al-Hatamleh, M., Hatmal, M., Smadi, O., Taha, M. O., Oweida, A. J., Boer, J. C., Mohamud, R., & Plebanski, M. “Comprehensive Structural and Molecular Comparison of Spike Proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, and Their Interactions with ACE2”, Cells, Vol. 9, Issue.12, pp.2638, 2020. https://doi.org/10.3390/cells9122638
[3] Ke, Z., Oton, J., Qu, K., Cortese, M., Zila, V., McKeane, L., Nakane, T., Zivanov, J., Neufeldt, C. J., Cerikan, B., Lu, J. M., Peukes, J., Xiong, X., Kräusslich, H. G., Scheres, S., Bartenschlager, R., & Briggs, J. “Structures and distributions of SARS-CoV-2 spike proteins on intact virions”, Nature, Vol.588, Issue.7838, pp.498–502, 2020. https://doi.org/10.1038/s41586-020-2665-2.
[4] V`kovski, P., Kratzel, A., Steiner, S., Stalder, H., & Thiel, V. “Coronavirus biology and replication: implications for SARS-CoV-2”,Nature reviews. Microbiology, Vol. 19, Issue.3, 155–170, 2021.https://doi.org/10.1038/s41579-020-00468-6.
[5] Malik Y. A. “Properties of Coronavirus and SARS-CoV-2”, The Malaysian journal of pathology, Vol.42, Issue. 1, pp.3–11, 2020.
[6] Xia X. “ Domains and Functions of Spike Protein in Sars-Cov-2 in the Context of Vaccine Design”,Viruses, Vol. 13, Issue.1, pp.109, 2021. https://doi.org/10.3390/v13010109.
[7] Wang, M. Y., Zhao, R., Gao, L. J., Gao, X. F., Wang, D. P., & Cao, J. M. “SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development”, Frontiers in cellular and infection microbiology, Vol.10, pp.587269. 2020. https://doi.org/10.3389/fcimb.2020.587269.
[8] Kinobe, R. T., & Owens, L. “A systematic review of experimental evidence for antiviral effects of ivermectin and an in silico analysis of ivermectin`s possible mode of action against SARS-CoV-2”, Fundamental & clinical pharmacology, Vol. 35, Issue.2, pp.260–276, 2021.https://doi.org/10.1111/fcp.12644.
[9] Junior, A. G., Tolouei, S., Dos Reis Lívero, F. A., Gasparotto, F., Boeing, T., & de Souza, P. “Natural Agents Modulating ACE-2: A Review of Compounds with Potential against SARS-CoV-2 Infections, Current pharmaceutical design, Vol.27, Issue.13, pp. 1588–1596, 2021. https://doi.org/10.2174/1381612827666210114150607
[10] Artese, A., Svicher, V., Costa, G., Salpini, R., Di Maio, V. C., Alkhatib, M., Ambrosio, F. A., Santoro, M. M., Assaraf, Y. G., Alcaro, S., & Ceccherini-Silberstein, F. “Current status of antivirals and druggable targets of SARS CoV-2 and other human pathogenic coronaviruses, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy,Vol. 53, pp.100721. 2020. https://doi.org/10.1016/j.drup.2020.100721.
[11] Meyer, A., & Imming, P. “Benzylisoquinoline alkaloids from the papaveraceae: the heritage of Johannes Gadamer (1867-1928)” Journal of natural products, Vol. 74, Issue.11, pp. 2482–2487. https://doi.org/10.1021/np2005049
[12] Weber, C., & Opatz, T. “Bisbenzylisoquinoline Alkaloids. The Alkaloids,Chemistry and biology, Vol. 81, pp.1–114, 2019. https://doi.org/10.1016/bs.alkal.2018.07.001
[13] He, C. L., Huang, L. Y., Wang, K., Gu, C. J., Hu, J., Zhang, G. J., Xu, W., Xie, Y. H., Tang, N., & Huang, A. L. “Identification of bis-benzylisoquinoline alkaloids as SARS-CoV-2 entry inhibitors from a library of natural products”, Signal transduction and targeted therapy, Vol.6,Issue.1, pp.131, 2021. https://doi.org/10.1038/s41392-021-00531-5
[14] Narayana, K. R., Reddy, M. S., Chaluvadi, M. R., & Krishna, D. R."Bioflavonoids classification, pharmacological, biochemical effects and therapeutic potential." Indian journal of pharmacology Vol. 33,Issue.1 pp. 2-16, 2001.
[15] Batool, F., Mughal, E. U., Zia, K., Sadiq, A., Naeem, N., Javid, A., Ul-Haq, Z., & Saeed, M. “Synthetic flavonoids as potential antiviral agents against SARS-CoV-2 main protease”,Journal of biomolecular structure & dynamics, pp.1–12, 2020. https://doi.org/10.1080/07391102.2020.1850359
[16] Gogoi, N., Chowdhury, P., Goswami, A. K., Das, A., Chetia, D., & Gogoi, B. “Computational guided identification of a citrus flavonoid as potential inhibitor of SARS-CoV-2 main protease”, Molecular diversity, Vol.25, Issue.3, pp.1745–1759, 2021. https://doi.org/10.1007/s11030-020-10150-x.
[17] Trott, O., & Olson, A. J. “AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading”, Journal of computational chemistry, Vol.31, Issue.2, ,pp. 455–461, 2010. https://doi.org/10.1002/jcc.21334.
[18] Dallakyan, S., & Olson, A. J. “ Small-molecule library screening by docking with PyRx”, Methods in molecular biology (Clifton, N.J.), Vol.1263, pp.243–250, 2015. https://doi.org/10.1007/978-1-4939-2269-7_19.
[19] Banerjee, R., Perera, L., & Tillekeratne, L. “Potential SARS-CoV-2 main protease inhibitors”,Drug discovery today, Vol. 26, Issue.3,pp. 804–816, 2021.https://doi.org/10.1016/j.drudis.2020.12.005.
[20] Ullrich, S., & Nitsche, C. “The SARS-CoV-2 main protease as drug target”, Bioorganic & medicinal chemistry letters, Vol.30, Issue.17, pp.127377, 2020. https://doi.org/10.1016/j.bmcl.2020.127377.
[21] Wang, Y. C., Yang, W. H., Yang, C. S., Hou, M. H., Tsai, C. L., Chou, Y. Z., Hung, M. C., & Chen, Y. “ Structural basis of SARS-CoV-2 main protease inhibition by a broad-spectrum anti-coronaviral drug,” American journal of cancer research, Vol.10, Issue.8, pp. 2535–2545, 2020.
[22] Coelho, C., Gallo, G., Campos, C. B., Hardy, L., & WĂĽrtele, M. Biochemical screening for SARS-CoV-2 main protease inhibitors. PloS one, Vol. 15, Issue.10, pp.e0240079, 2020. https://doi.org/10.1371/journal.pone.0240079.
[23] Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. “AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility”, Journal of computational chemistry, Vol. 30,Issue.6,pp. 2785–2791, 2009. https://doi.org/10.1002/jcc.21256.
[24] Artemova, S., Jaillet, L., & Redon, S. “Automatic molecular structure perception for the universal force field”, Journal of computational chemistry, Vol. 37, Issue.13, pp.1191–1205, 2016. https://doi.org/10.1002/jcc.24309.
[25] Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. “UCSF Chimera--a visualization system for exploratory research and analysis. Journal of computational chemistry, Vol. 25, Issue.13, pp.1605–1612, 2004. https://doi.org/10.1002/jcc.20084.
[26] Kaplan, W., & Littlejohn, T. G. “Swiss-PDB Viewer (Deep View). Briefings in bioinformatics, Vol.2, Issue.2,pp. 195–197, 2001. https://doi.org/10.1093/bib/2.2.195.
[27] Kemmish, H., Fasnacht, M., & Yan, L. “Fully automated antibody structure prediction using BIOVIA tools: Validation study”, PloS one, Vol. 12, Issue.5, pp.e0177923, 2017.