In Silico Identification of Active Phytochemicals against COVID-19 by Targeting the SARS-CoV-2 Spike Glycoprotein Through Molecular Docking: A Drug Repurposing Approach
Keywords:
Novel Coronavirus, Phytochemicals, SARS-CoV-2, ADME, Drug likeliness, Molecular dockingAbstract
The spread of coronavirus disease (COVID-19) has become one of the most significant pandemics in modern human history, affecting more than 70 million people worldwide. Currently, only a few fda-approved drugs have suggested fighting the infection, in the absence of a specific antiviral treatment. Thus, repurposing the presently available drugs or using plant-based bioactive compounds can be the fastest possible solution. In this study, the computational methodology of molecular docking techniques was performed to screen and identify the viable potent inhibitors against the SARS-CoV-2 spike protein from a library of 200 active phytochemicals, based on their highest binding affinity towards the target protein. Later, the binding affinities of these phytochemicals were compared with that of the fda-approved drug fluvoxamine, which is currently in use against the mild COVID-19 patients. Out of these, 86 phytochemicals that exhibited better binding energy of value ≤-7.00kcal/mol, is selected for adme (absorption, distribution, metabolism, and excretion) analysis and drug likeliness studies to check the feasibility of these compounds. Wherein, 79 out of 86 phytochemicals showed a better theoretical affinity with sufficiently bearable adme properties. Thus, they can be the lead molecule for further investigation and validation processes towards developing natural inhibitors against the SARS-CoV-2 virus.
Downloads
References
D. Cucinotta and M. Vanelli, “WHO declares COVID-19 a pandemic,” Acta Biomed., vol. 91, no. 1, pp. 157–160, 2020, doi: 10.23750/abm.v91i1.9397.
C. Huang et al., “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China,” Lancet, 2020, doi: 10.1016/S0140-6736(20)30183-5.
World Health Organization, “Naming the coronavirus disease (COVID-19) and the virus that causes it,” World Heal. Organ., 2020.
WHO, “COVID-19 Weekly Epidemiological Update Global epidemiological situation,” no. December, 2020, [Online]. Available: https://www.who.int/publications/m/item/weekly-epidemiological-update---15-december-2020.
A. E. Gorbalenya et al., “The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2,” Nat. Microbiol., vol. 5, no. 4, pp. 536–544, 2020, doi: 10.1038/s41564-020-0695-z.
A. R. Fehr and S. Perlman, “Coronaviruses: An overview of their replication and pathogenesis,” in Coronaviruses: Methods and Protocols, 2015.
Y. Bai et al., “Presumed Asymptomatic Carrier Transmission of COVID-19,” JAMA - Journal of the American Medical Association. 2020, doi: 10.1001/jama.2020.2565.
M. Cascella, M. Rajnik, A. Cuomo, S. C. Dulebohn, and R. Di Napoli, Features, Evaluation and Treatment Coronavirus (COVID-19). 2020.
R. Lu et al., “Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding,” Lancet, 2020, doi: 10.1016/S0140-6736(20)30251-8.
Y. Shi et al., “An overview of COVID-19,” Journal of Zhejiang University: Science B. 2020, doi: 10.1631/jzus.B2000083.
Z. Song et al., “From SARS to MERS, thrusting coronaviruses into the spotlight,” Viruses. 2019, doi: 10.3390/v11010059.
M. Pandit, “In silico studies reveal potential antiviral activity of phytochemicals from medicinal plants for the treatment of COVID-19 infection,” pp. 1–38, 2020, doi: 10.21203/rs.3.rs-22687/v1.
A. A. T. Naqvi et al., “Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach,” Biochimica et Biophysica Acta - Molecular Basis of Disease. 2020, doi: 10.1016/j.bbadis.2020.165878.
A. C. Walls, Y. J. Park, M. A. Tortorici, A. Wall, A. T. McGuire, and D. Veesler, “Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein,” Cell, 2020, doi: 10.1016/j.cell.2020.02.058.
B. Coutard, C. Valle, X. de Lamballerie, B. Canard, N. G. Seidah, and E. Decroly, “The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade,” Antiviral Res., 2020, doi: 10.1016/j.antiviral.2020.104742.
P. Kumari, C. Kumari, and P. S. Singh, “Phytochemical Screening of Selected Medicinal Plants for Secondary Metabolites,” Int. J. Life- Sci. Sci. Res., 2017, doi: 10.21276/ijlssr.2017.3.4.9.
H. Krishnamachari and N. V, “Phytochemical Analysis and Antioxidant Potential of Cucumis Melo Seeds,” Int. J. Life-Sciences Sci. Res., 2017, doi: 10.21276/ijlssr.2017.3.1.19.
A. N. Panche, A. D. Diwan, and S. R. Chandra, “Flavonoids: An overview,” Journal of Nutritional Science. 2016, doi: 10.1017/jns.2016.41.
S. Kumar and A. K. Pandey, “Chemistry and biological activities of flavonoids: An overview,” The Scientific World Journal. 2013, doi: 10.1155/2013/162750.
L. Shaffer, “15 drugs being tested to treat COVID-19 and how they would work,” Nat. Med., 2020, doi: 10.1038/d41591-020-00019-9.
E. J. Lenze et al., “Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients with Symptomatic COVID-19: A Randomized Clinical Trial,” JAMA - J. Am. Med. Assoc., 2020, doi: 10.1001/jama.2020.22760.
A. M. Dar and S. Mir, “Molecular Docking: Approaches, Types, Applications and Basic Challenges,” J. Anal. Bioanal. Tech., 2017, doi: 10.4172/2155-9872.1000356.
G. M. Morris and M. Lim-Wilby, “Molecular docking,” Methods Mol. Biol., 2008, doi: 10.1007/978-1-59745-177-2_19.
L. C. Mishra, B. B. Singh, and S. Dagenais, “Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): A review,” Alternative Medicine Review. 2000.
W. Vanden Berghe, L. Sabbe, M. Kaileh, G. Haegeman, and K. Heyninck, “Molecular insight in the multifunctional activities of Withaferin A,” Biochemical Pharmacology. 2012, doi: 10.1016/j.bcp.2012.08.027.
F. Wu, H. Wang, J. Li, J. Liang, and S. Ma, “Homoplantaginin modulates insulin sensitivity in endothelial cells by inhibiting inflammation,” Biol. Pharm. Bull., 2012, doi: 10.1248/bpb.b110586.
X. J. Qu et al., “Protective effects of Salvia plebeia compound homoplantaginin on hepatocyte injury,” Food Chem. Toxicol., 2009, doi: 10.1016/j.fct.2009.04.032.
S. Bang, W. Li, T. K. Q. Ha, C. Lee, W. K. Oh, and S. H. Shim, “Anti-influenza effect of the major flavonoids from Salvia plebeia R.Br. via inhibition of influenza H1N1 virus neuraminidase,” Nat. Prod. Res., 2018, doi: 10.1080/14786419.2017.1326042.
S. H. Park et al., “Sage weed (Salvia plebeia) extract antagonizes foam cell formation and promotes cholesterol efflux in murine macrophages,” Int. J. Mol. Med., 2012, doi: 10.3892/ijmm.2012.1103.
C. S. Graebin, “The Pharmacological Activities of Glycyrrhizinic Acid (‘Glycyrrhizin’) and Glycyrrhetinic Acid,” 2018.
S. Jiang et al., “Antibacterial bibenzyl derivatives from the tubers of Bletilla striata,” Elsevier, 2019.
D. Xu, Y. Pan, and J. Chen, “Chemical constituents, pharmacologic properties, and clinical applications of bletilla striata,” Front. Pharmacol., 2019, doi: 10.3389/fphar.2019.01168.
D. O. Ha, C. U. Park, M. J. Kim, and J. H. Lee, “Antioxidant and prooxidant activities of β-carotene in accelerated autoxidation and photosensitized model systems,” Food Sci. Biotechnol., 2012, doi: 10.1007/s10068-012-0078-1.
S. Toma, P. L. Losardo, M. Vincent, and R. Palumbo, “Effectiveness of β-carotene in cancer chemoprevention,” European Journal of Cancer Prevention. 1995, doi: 10.1097/00008469-199506000-00002.
S. Bulle, H. Reddyvari, V. Nallanchakravarthula, and D. R. Vaddi, “Therapeutic Potential of Pterocarpus santalinus L .: An Update,” pp. 43–49, 2016, doi: 10.4103/0973-7847.176575.
C. A. Lipinski, F. Lombardo, B. W. Dominy, and P. J. Feeney, “Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings,” vol. 46, pp. 3–26, 2001.
E. F. Pettersen et al., “UCSF Chimera - A visualization system for exploratory research and analysis,” J. Comput. Chem., 2004, doi: 10.1002/jcc.20084.
N. Guex and M. C. Peitsch, “SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling,” Electrophoresis, 1997, doi: 10.1002/elps.1150181505.
W. Tian, C. Chen, X. Lei, J. Zhao, and J. Liang, “CASTp 3.0: Computed atlas of surface topography of proteins,” Nucleic Acids Res., 2018, doi: 10.1093/nar/gky473.
Morris G.M. and Dallakyan S., “AutoDock — AutoDock,” 02-27, 2013.
G. M. Morris et al., “Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity,” J. Comput. Chem., 2009.
R. A. Laskowski and M. B. Swindells, “LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery,” J. Chem. Inf. Model., 2011, doi: 10.1021/ci200227u.
B. Jayaram, T. Singh, G. Mukherjee, A. Mathur, S. Shekhar, and V. Shekhar, “Sanjeevini: a freely accessible web-server for target directed lead molecule discovery.,” BMC Bioinformatics, 2012, doi: 10.1186/1471-2105-13-S17-S7.
C. A. Lipinski, “Lead- and drug-like compounds: The rule-of-five revolution,” Drug Discovery Today: Technologies. 2004, doi: 10.1016/j.ddtec.2004.11.007.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
editor@ijrasb.com 