Mikrobiol. Z. 2021; 83(2):82-92.
doi: https://doi.org/10.15407/microbiolj83.02.082

Molecular Docking of SARS-CoV-2 Nucleocapsid Protein with Angiotensin-Converting Enzyme II

A.A. Dawood1, M.A.A. Altobje2, Z.T. Al-Rrassam3

1Department of Anatomy, College of Medicine
University of Mosul, Mosul, Iraq

2Department of Biology, College of Science
University of Mosul, Mosul, Iraq

3Department of Biophysics, College of Science
University of Mosul, Mosul, Iraq

SARS-CoV-2 remains life-threatening human pathogen witnessed in the present world. Purpose. The key objective of this research was to incorporate a bioinformatics technique to forecast the molecular docking of the ACE2-associated SARS-CoVs nucleocapsid protein. Methods. Different bioinformatics tools were used in this study in order to compare the chemical structures with their biological behaviour at the levels of atoms and the ligand-binding affinity. This research sought to investigate new data analysis. Results. It was computed the basic 2D structure that occurs in all models, requiring ion ligand binding sites to be predicted. The highlights of the analysis and the associated characteristics are largely responsible for nucleocapsid protein and ACE2 receptor that can be further changed for improved binding and selectivity. Conclusions. The precise functional importance of protein-protein docking cannot be established. But the detection of molecular docking can aid in self-association proteins in our summary, serving as a regulatory switch for the protein’s localization.

Keywords: COVID-19, SARS-CoV-2, angiotensin-converting enzyme II (ACE2), nucleocapsid, molecular docking, receptor-binding domain (RBD) protein, RMSD.

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  1. Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol. 2020; 92:418–423. https://doi.org/10.1002/jmv.25681
  2. Gralinski LE, Menachery D. Return of the Coronavirus: 2019-nCoV. Viruses. 2020; 12:135. https://doi.org/10.3390/v12020135
  3. Liu W, Morse S, Lalonde T, Xu S. Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV. Chembiochem. 2020; 21:730–738. https://doi.org/10.1002/cbic.202000047
  4. Dawood A. Mutated COVID-19, May Foretells Mankind in a Great Risk in The Future. N Mic N Inf. 2020. https://doi.org/10.1016/j.nmni.2020.100673
  5. McBride R, Zyl M, Fielding C. The coronavirus nucleocapsid is a multifunctional protein. Viruses. 2014; 6:2991–3018. https://doi.org/10.3390/v6082991
  6. Wurm T, Chen H, Hodgson T, Britton P, Brooks G, Hiscox G.A. Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division. J Virol. 2001; 75:9345–9356. https://doi.org/10.1128/JVI.75.19.9345-9356.2001
  7. You J, Dove K, Enjuanes L, DeDiego L, Alvarez E, Howell J, et al. Subcellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein. J Gen Virol. 2005; 86(12):3303–3310. https://doi.org/10.1099/vir.0.81076-0
  8. Song W, Gui M, Wang X, Xiang Y. Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog. 2018; 14:e1007236. https://doi.org/10.1371/journal.ppat.1007236
  9. 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; 581:215–220. https://doi.org/10.1038/s41586-020-2180-5
  10. He J, Tao H, Yan Y, Huang S-Y, Xiao Y. Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2. Viruses. 202; 12:428. https://doi.org/10.3390/v12040428
  11. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395:565–574. https://doi.org/10.1016/S0140-6736(20)30251-8
  12. Gui M, Song W, Zhou H, Xu J, Chen S, Xiang Y, et al. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res. 2017; 27:119–129. https://doi.org/10.1038/cr.2016.152
  13. Dawood A. Identification of CTL and B-cell epitopes in the Nucleocapsid Phosphoprotein of COVID-19 using Immunoinformatics. Mic J. 2021; 83(1):1–9. https://doi.org/10.15407/microbiolj83.01.078
  14. Pierce BG, Wiehe K, Hwang H, Kim B-H, Vreven T, Weng Z. ZDOCK server: interactive docking prediction of protein-protein complexes and symmetric multimers. Bioinformatics. 2014; 30:1771–3. https://doi.org/10.1093/bioinformatics/btu097
  15. Wan Y, Shang J, Graham R, Baric RS, Li L. Receptor recognition by a novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J Virol. 2020; 94(7):e00127-20. https://doi.org/10.1128/JVI.00127-20
  16. Dawood A, Altobje M. Inhibition of N-linked Glycosylation by Tunicamycin May Contribute to The Treatment of SARS-CoV-2. Microbiol Path. 2020; 149:104586. https://doi.org/10.1016/j.micpath.2020.104586
  17. Walls C, Park J, Tortorici A, Wall A, McGuire T, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020; 181(2):281–292. https://doi.org/10.1016/j.cell.2020.02.058
  18. Dharma K, Sharun K, Tiwari R, Dadar M, Malik S, Singh P, Chaicumpa W. COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics. Hum Vaccin Immunother. 2020:1–7. https://doi.org/10.1080/21645515.2020.1735227
  19. Chen Y, Guo Y, Pan Y, Zhao ZJ. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. 2020; 17: S0006-291X(20)30339-9.
  20. Lin L, Shao J, Sun M, Liu J, Xu G, Zhang X, et al. Identification of phosphorylation sites in the nucleocapsid protein (N protein) of SARS-coronavirus. Int J Mass Spect. 2007; 268:296–303. https://doi.org/10.1016/j.ijms.2007.05.009
  21. Dawood A, Alnori H. Tunicamycin Anticancer Drug May Reliable to Treat Coronavirus Disease-19. OAMJMS. 2020; 8(T1):129–133. https://doi.org/10.3889/oamjms.2020.4954
  22. Velavan P, Meyer G. The COVID-19 epidemic. Trop Med Int Health. 2020; 25(3):278–280. https://doi.org/10.1111/tmi.13383
  23. Hasan A, Hossain M, Alam J. A computational assay to design an epitope-based Peptide vaccine against Saint Louis encephalitis virus. Bioinformatics and Biology insights. 2013; 7:BBI-S13402. https://doi.org/10.4137/BBI.S13402
  24. Thomas J, Maria O, Serrano L, Pujo H, Rangel R. Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: An in silico analysis. EXCLI J. 2020; 19:410–417.
  25. Lu G, Wang Q Gao GF. Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond. Trends Microbiol. 2015; 23:468–78. https://doi.org/10.1016/j.tim.2015.06.003
  26. Luan J, Lu Y, Jin X, Zhang L. Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection. Biochem Biophys Res Comm. 2020; 526(1):165–9. https://doi.org/10.1016/j.bbrc.2020.03.047
  27. Ibrahim IM, Abdelmalek DH, Elshahat ME, Elfiky AA. COVID-19 spike-host cell receptor GRP78 binding site prediction. J Infect. 2020; 80(5):554–62. https://doi.org/10.1016/j.jinf.2020.02.026
  28. Narkhede R, Cheke R, Ambhore J, Shinde S. The Molecular Docking Study of Potential Drug Candidates Showing Anti-COVID-19 Activity by Exploring of Therapeutic Targets of SARS-CoV-2. EJMO. 2020; 4(3):185–195.
  29. González-Paz1 L, Lossada C, Moncayo L, Romero F, Paz J, Vera-Villalobos J, et al. Molecular Docking and Molecular Dynamic Study of two Viral Proteins associated with SARS-CoV-2 with Ivermectin. Preprints.
  30. Gomez D, Huber K, Klumpp S. On protein folding in crowded conditions. J Phys Chemis Let. 2019; 10(24):7650–7656. https://doi.org/10.1021/acs.jpclett.9b02642
  31. Peele A, Durthi C, Srihansa T, Krupanidhi S, Sai A, Babu D, et al. Molecular docking and dynamic simulations for antiviral compounds against SARS-CoV-2: A computational study. Inform. Med. Unlo. 2020; 19:100345. https://doi.org/10.1016/j.imu.2020.100345
  32. Cubuk H, and Ozbil M. Comparison of Clinically Approved Molecules on SARS-CoV-2 Drug Target Proteins: A Molecular Docking Study. ChemRxiv. 2020. https://doi.org/10.26434/chemrxiv.12090828.v2
  33. Yu R, Chen L, Lan R, Shen R, Li P. Computational screening of antagonists against the SARS-CoV-2 (COVID-19) coronavirus by molecular docking. Int J Antmic Ag. 2020; 7:29. https://doi.org/10.1016/j.ijantimicag.2020.106012