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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Neutralization of SARS-CoV-2 Spike Protein via Natural Compounds: A Multilayered High Throughput Virtual Screening Approach

Author(s): Anupam Dhasmana, Vivek K. Kashyap, Swati Dhasmana, Sudhir Kotnala, Shafiul Haque, Ghulam Md. Ashraf, Meena Jaggi, Murali M. Yallapu and Subhash C. Chauhan*

Volume 26, Issue 41, 2020

Page: [5300 - 5309] Pages: 10

DOI: 10.2174/1381612826999200820162937

Price: $65

Abstract

Background: Previously human society has faced various unprecedented pandemics in the history and viruses have majorly held the responsibilities of those outbreaks. Furthermore, due to amplified global connection and speedy modernization, epidemic outbreaks caused by novel and re-emerging viruses signify potential risk to community health. Despite great advancements in immunization and drug discovery processes, various viruses still lack prophylactic vaccines and efficient antiviral therapies. Although, vaccine is a prophylaxes option, but it cannot be applied to infected patients, hence therapeutic interventions are urgently needed to control the ongoing global SARS- CoV-2 pandemic condition. To spot the novel antiviral therapy is of decisive importance and Mother Nature is an excellent source for such discoveries.

Methodology: In this article, prompt high through-put virtual screening for vetting the best possible drug candidates from natural compounds’ databases has been implemented. Herein, time tested rigorous multi-layered drug screening process to narrow down 66,969 natural compounds for the identification of potential lead(s) is implemented. Druggability parameters, different docking approaches and neutralization tendency of the natural products were employed in this study to screen the best possible natural compounds from the digital libraries.

Conclusion: The results of this study conclude that compounds PALA and HMCA are potential inhibitors of SARS-CoV-2 spike protein and can be further explored for experimental validation. Overall, the methodological approach reported in this article can be suitably used to find the potential drug candidates against SARS-CoV2 in the burning situation of COVID-19 with less expenditure and a concise span of time.

Keywords: SARS-CoV-2, viral spike protein, Human Angiotensin Convertase Enzyme-2 (hACE-2), Natural Compounds, High Throughput Virtual Screening (HTVS), ADMET and neutralization potential.

« Previous Next »
[1]
Pascarella G, Strumia A, Piliego C, et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med 2020 In press
[2]
Jogalekar MP, Veerabathini A, Gangadaran P. Novel 2019 coronavirus: Genome structure, clinical trials, and outstanding questions. Exp Biol Med (Maywood) 2020; 254(11): 964-9.
[3]
Kim E, Erdos G, Huang S, et al. Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development. EBioMedicine 2020 In press
[4]
Li W, Moore MJ, Vasllieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Cell Mol Life Sci 2004; 61(21): 2738-43.
[http://dx.doi.org/10.1038/nature02145]
[5]
Ge XY, Li JL, Yang X. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 2013; 503: 535-8.
[6]
Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 2020; 581(7807): 215-20.
[http://dx.doi.org/10.1038/s41586-020-2180-5]
[7]
Cava C, Bertoli G, Castiglioni I. In silico discovery of candidate drugs against covid-19. Viruses 2020; 12(4): 404.
[8]
Chabot I, Goetghebeur MM, Grégoire JP. The societal value of universal childhood vaccination. Vaccine 2004; 22(15-16): 1992-2005.
[http://dx.doi.org/10.1016/j.vaccine.2003.10.027]
[9]
Huang J, Song W, Huang H, Sun Q. Pharmacological Therapeutics Targeting RNA-Dependent RNA Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-19. J Clin Med 2020; 9(4): 1131.
[10]
Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet 2020; 395(10223): e30-1.
[11]
Stafford EG, Riviere JE, Xu X, Kawakami J, Wyckoff GJ, Jaberi-Douraki M. Pharmacovigilance in patients with diabetes: A datadriven analysis identifying specific RAS antagonists with adverse pulmonary safety profiles that have implications for COVID-19 morbidity and mortality. J Am Pharm Assoc (2003) 2020; 60(6): e145-52.
[PMID: 32561317]
[12]
Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Engl J Med 2020; 382: 1653-9.
[http://dx.doi.org/10.1056/NEJMsr2005760]
[13]
Burrell LM, Johnston CI, Tikellis C, Cooper ME. ACE2, a new regulator of the renin-angiotensin system. Trends Endocrinol Metab 2004; 15(4): 166-9.
[14]
Jia H. Pulmonary Angiotensin-Converting Enzyme 2 (ACE2) and Inflammatory Lung Disease. Shock 2016; 46(3): 239-48.
[15]
Lei C, Qian K, Li T, et al. Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig. Nat Commun 2020; 2020(2070): 11.
[16]
Lin LT, Hsu WC, Lin CC. Antiviral natural products and herbal medicines. J Tradit Complement Med 2014; 4(1): 24-35.
[http://dx.doi.org/10.4103/2225-4110.124335]
[17]
Szklarczyk D, Morris JH, Cook H, et al. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res 2017; 45(D1): D362-68.
[18]
Anukriti Dhasmana A. Investigation of precise molecular mechanistic action of tobacco-associated carcinogen `NNK´ induced carcinogenesis: A system biology approach. Genes (Basel) 2019; 10(8): 564.
[19]
Bindea G, Mlecnik B, Hackl H, et al. ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 2009; 25(8): 1091-3.
[http://dx.doi.org/10.1093/bioinformatics/btp101]
[20]
Chen CYC. TCM Database@Taiwan: The world’s largest traditional Chinese medicine database for drug screening In Silico. PLoS One 2011; 6(1)
[21]
Zeng X, Zhang P, He W, et al. Natural product activity and species source database for natural product research, discovery and tool development. Nucleic Acids Res 2018; 46: 1217-22.
[22]
Diller DJ, Merz KM. High throughput docking for library design and library prioritization. Proteins 2001; 43(2): 113-24.
[http://dx.doi.org/10.1002/1097-0134(20010501)43:2<113:AID-PROT1023>3.0.CO;2-T]
[23]
Diller DJ, Li R. Kinases, Homology Models, and High Throughput Docking. J Med Chem 2003; 46(22): 4638-47.
[24]
Rao SN, Head MS, Kulkarni A, LaLonde JM. Validation studies of the site-directed docking program LibDock. J Chem Inf Model 2007; 47(6): 2159-71.
[http://dx.doi.org/10.1021/ci6004299]
[25]
Wu G, Robertson DH, Brooks CL, Vieth M. Detailed analysis of grid-based molecular docking: A case study of CDOCKER - A CHARMm-based MD docking algorithm. J Comput Chem 2003; 24(13): 1549-62.
[26]
Erickson JA, Jalaie M, Robertson DH, Lewis RA, Vieth M. Lessons in molecular recognition: the effects of ligand and protein flexibility on molecular docking accuracy. J Med Chem 2004; 47(1): 45-55.
[http://dx.doi.org/10.1021/jm030209y PMID: 14695819]
[27]
Mashiach E, Schneidman-Duhovny D, Andrusier N, Nussinov R, Wolfson HJ. FireDock: a web server for fast interaction refinement in molecular docking. Nucleic Acids Res 2008; 36W229-32
[http://dx.doi.org/10.1093/nar/gkn186]
[28]
Dhasmana A, Jamal QMS, Gupta R, et al. Titanium dioxide nanoparticles provide protection against polycyclic aromatic hydrocarbon BaP and chrysene-induced perturbation of DNA repair machinery: A computational biology approach. Biotechnol Appl Biochem 2016; 63(4): 497-513.
[http://dx.doi.org/10.1002/bab.1388]
[29]
Kuster GM, Pfister O, Burkard T, et al. SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19? Eur Heart J 2020; 41(19): 1801-3.
[30]
Bruntz RC, Lindsley CW, Brown HA. Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer. Pharmacol Rev 2014; 66(4): 1033-79.
[http://dx.doi.org/10.1124/pr.114.009217]
[31]
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001; 46(1-3): 3-26.
[32]
McInnes C. Virtual screening strategies in drug discovery. Curr Opin Chem Biol 2007; 11(5): 494-502.
[http://dx.doi.org/10.1016/j.cbpa.2007.08.033]
[33]
Bajorath J. Integration of virtual and high-throughput screening. Nat Rev Drug Discov 2002; 1: 882-94.
[http://dx.doi.org/10.1038/nrd941]
[34]
Mortelmans K, Zeiger E. The Ames Salmonella/microsome mutagenicity assay. Mutat Res 2000; 455(1-2): 29-60.
[35]
Gombar V, Silver I, Zhao Z. Role of ADME Characteristics in Drug Discovery and Their In Silico Evaluation: In Silico Screening of Chemicals for their Metabolic Stability. Curr Top Med Chem 2005; 3(11): 1205-25.
[36]
Scheife RT. Protein binding: What does it mean? DICP 1989; 23 Suppl. 7-8: S27-31.
[37]
Wyde PR, Moore DK, Pimentel DM, Blough HA. Evaluation of the antiviral activity of N-(phosphonoacetyl)-l-aspartate against paramyxoviruses in tissue culture and against respiratory syncytial virus in cotton rats. Antiviral Res 1995; 27(1-2): 59-69.
[38]
Ohue-Kitano R, Taira S, Watanabe K, et al. 3-(4-Hydroxy-3-methoxyphenyl)propionic acid produced from 4-Hydroxy-3-methoxycinnamic acid by gut microbiota improves host metabolic condition in diet-induced obese mice. Nutrients 2019; 11(5): 1036.
[39]
Lamers MM, Beumer J, van der Vaart J, et al. SARS-CoV-2 Productively Infects Human Gut Enterocytes. Science 2020; 369(6499): 50-4.

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