Volume 8, Issue 3, September 2020, Page: 42-52
Immunoinformatics Design of Novel Multi-Epitope Subunit Vaccine for SARS-CoV-2 by Exploring Virus Conserved Sequences of the Spike Glycoproteins
Itemobong Ekaidem, Department of Chemical Pathology, University of Uyo, Uyo, Nigeria; Institute of Biomedical Research and Innovations, University of Uyo, Uyo, Nigeria
Anietie Moses, Institute of Biomedical Research and Innovations, University of Uyo, Uyo, Nigeria; Department of Medical Microbiology and Parasitology, University of Uyo, Uyo, Nigeria
Youtchou Tatfeng, Institute of Biomedical Research and Innovations, University of Uyo, Uyo, Nigeria; Deparment of Medical Laboratory Science, Niger Delta University, Wilberforce Island, Nigeria
Received: Jul. 6, 2020;       Accepted: Jul. 21, 2020;       Published: Oct. 27, 2020
DOI: 10.11648/j.iji.20200803.12      View  56      Downloads  62
Sars-CoV-2 infection also called COVID-19 is characterized by fever and signs of acute respiratory distress syndrome (ARDS). It is currently a global pandemic with high mortality rate in those with severe disease. Lack of effective vaccine and approved drug for treatment created a disastrous condition among the global communities. This study was designed as a step ahead in the path of protein-based subunit vaccine development. The primary amino acid sequence of SARS-CoV-2 spike glycoprotein was used to design a protein subunit vaccine construct. The molecular weight of vaccine protein was 58.4 kDa with a total number of 8170 atoms and 584 amino acid residues. The theoretical pI was found to be 8.54 showing its slightly basic nature while the total number of negative and positive charged residues were 29 and 33 respectively. The peptide vaccine construct has 147 (25.17%) polar residues and 375 (64.21%) hydrophobic residues. The vaccine construct has cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) and B cell epitopes of varying lengths having great potential to stimulate high levels of IFN-γ production. It has potent antigenic properties but lacked allergenicity. It is stable and have a good binding affinity for the TLR-4 receptor. In general, this modelling applied a series of immunoinformatics tools in a sequential manner to find an effective vaccine that may be used effectively in fighting against the COVID-19 pandemic. This modelling, however, needs real life experimental validation to prove the workability of the computational work.
Sars-CoV-2, COVID 19, Subunit Vaccine, Immunoinformatics, Multi-Epitopes Vaccine
To cite this article
Itemobong Ekaidem, Anietie Moses, Youtchou Tatfeng, Immunoinformatics Design of Novel Multi-Epitope Subunit Vaccine for SARS-CoV-2 by Exploring Virus Conserved Sequences of the Spike Glycoproteins, International Journal of Immunology. Vol. 8, No. 3, 2020, pp. 42-52. doi: 10.11648/j.iji.20200803.12
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WHO (2020). Novel Coronavirus (2019-nCoV) Situation Report 23. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200212-sitrep-23-ncov.pdf?sfvrsn=41e9fb78_4.
Chan, J. F., Lau, S. K., To, K. K., Cheng, V. C., Woo, P. C., Yuen, K. Y. (2015) Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like dis-ease. Clin Microbiol Rev 28 (2): 465–522.
Elfiky, A. A., Mahdy, S. M., Elshemey, W. M. (2017) Quantitative structure-activity relation-ship and molecular docking revealed a potency of anti-hepatitis C virus drugs against human corona viruses. J Med Virol; 89 (6): 1040–1047.
Chan, J. F. W., Kok, K. H., Zhu, Z., Chu, H., To, K. K. W., Yuan, S. F., Yuen, K. Y. (2020) Genomic characterization of the 2019 novel humanpathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan, Emerging Microbes & Infections, 9: 1, 221-236, http://dx.doi.org/10.1080/22221751.2020.1719902.
Jiang, S., Du, L. & Shi, Z. (2020) An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerg. Microbes Infect. 9, 275–277.
Hoffman, M., Kleine-Weber, H., Schroeder, S., Kruger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N. H., Nitsche, A., Muller, M. A., Drosten, C., Pohlman, S. (2020) SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 181, 1–10.
Callaway, E. (2020) The race for coronavirus vaccines: a graphical guide. Nature 2020; 580: 576-577 doi: 10. 1038/d41586-020-01221-y.
Krammer, F. & Palese, P. (2015). Advances in the development of influenza virus vaccines. Nat Rev Drug Discov 14, 167-182.
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., et al. (2020). A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 382, 727-733.
Zaki, A. M., van Boheemen, S., Bestebroer, T. M., Osterhaus, A. D., Fouchier, R. A. (2012) Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 367, 1814–1820.
Walls, A. C., Park, Y. J., Tortorici, A. M., Wall, A., Andrew T. McGuire, A. T., Veesler, D. (2020) Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein Cell 180, 1–12 https://doi.org/10.1016/j.cell.2020.02.058.
Lan, J., Ge, J., Yu, J., Shan, S., Zhou, H., Fan, S., Zhang, Q., Shi, X., Wang, Q., Zhang, L., and Wang, X. (2020a). Crystal structure of the 2019-nCoV spike receptor-binding domain bound with the ACE2 receptor. bioRxiv, 2020.2002.2019.956235.
Khatoon, N., Pandey, R. K. & Prajapati, V. K. (2017) Exploring Leishmania secretory proteins to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach. Sci. Rep. 7, 8285, https://doi.org/10.1038/s41598-017-08842-w.
Larsen, M. V., Laundegaard, C., Lamberth, L., Buus, S., Lund, O., Nyelsen, M. (2007) Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinformatics 8, 424, https://doi.org/10.1186/1471-2105-8-424.
Pradhan, D., Yadav, M., Verma, R., Khan, N. S., Jena, L., Jain, A. K. (2017) Discovery of T-cell Driven Subunit Vaccines from Zika Virus Genome: An Immunoinformatics Approach. Interdiscip. Sci. 9, 468–477, https://doi: 10.1007/s12539-017-0238-3.
Black, M., Trent, A., Tirrell, M. & Olive, C. (2010) Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists. Expert Rev. Vaccines 9, 157–173, https://doi.org/10.1586/erv.09.160.
EL‐Manzalawy, Y., Dobbs, D. & Honavar, V. (2008) Predicting linear B‐cell epitopes using string kernels. J. Mol. Recogn. 21, 243–255.
Shi, J. Zhang, J., Li, S., Sun, J., Teng, Y., Wu, M., Li, J., Li, Y., Hu, N., Wang, H., Hu, Y. (2015) Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases. PLoS One 10, e0144475, https://doi.org/10.1371/journal.pone.0144475.
Magnan, C. N., Zeller, M., Kayala, M. A., Vigil, A., Randall, A., Felgner, P. L., Baldi, P. (2010) High-throughput prediction of protein antigenicity using protein microarray data Bioinformatics, 26 (23): 2936–2943, https://doi.org/10.1093/bioinformatics/btq551.
Dimitrov, I., Flower, D. R. & Doytchinova, I. (2013) AllerTOP - a server for in silico prediction of allergens. BMC Bioinformatics 14, S4–S4, https://doi.org/10.1186/1471-2105-14-S6-S4.
Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N., Stemberg, M. J. E. (2015) The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10: 845–858. doi: 10. 1038/nprot. 2015. 053.
Chander, S., Pandey, R. K., Penta, A., Choudhary, B. S., Sharma, M., Malik, R., Prajapati, V. K., Murugesan, S. (2017) Molecular docking and molecular dynamics simulation-based approach to explore the dual inhibitor against HIV-1 reverse transcriptase and Integrase. Comb. Chem. High Throughput Screen. 20, 1–13, https://doi.org/10.2174/1386207320666170615104703.
Pandey, R. K., Prajapati, P., Goyal, S., Grover, A. & Prajapati, V. K. (2016) Molecular Modeling and Virtual Screening Approach to Discover Potential Antileishmanial Inhibitors Against Ornithine Decarboxylase. Comb. Chem. High Throughput. Screen. 19, 813–823. http://doi:10.2174/1386207319666160907100134.
Heo, L., Park, H. & Seok, C. (2013) GalaxyRefine: Protein structure refinement driven by side-chain repacking. Nucleic Acids Res. 41, W384–388.
Craig, D. B. & Dombkowski, A. A. (2013) Disulfide by Design 2.0: a web-based tool for disulfide engineering in proteins. BMC Bioinformatics 14, 346, https://doi.org/10.1186/1471-2105-14-346.
Ali, M., Pandey, R. K., Khatoon, N., Narula, A. & Mishra, A. (2017) Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection. Sci. Rep. 7, 9232, https://doi.org/10.1038/s41598-017-09199-w.
Kozakov, D., Hall, D. R., Xia, B., Porter, K. A., Padhorny, D., Yueh, C., Beglov, D., Vajda, S. (2017) The ClusPro web server for protein-protein docking. Nature Protocols. 2017 Feb; 12 (2): 255-278.
Calis, J. J. A., Maybeno, M., Greenbaum, J. A., Weiskopf, D., DeSilva, A. D., Stte, A., Kesmir, C., Peters, B. (2013) Properties of MHC class I presented peptides that enhance immunogenicity. PLoS Comput. Biol. 9, e1003266, https://doi.org/10.1371/journal.pcbi.1003266.
Jordan, K. A. & Hunter, C. A. (2010) Regulation of CD8 (+) T Cell Responses to Infection With Parasitic Protozoa. Exp. Parasitol. 126, 318–325.
Moseman, E. A. & McGavern, D. B. (2013) The great balancing act: regulation and fate of antiviral T-cell interactions. Immunol. Rev. 255, 110–124.
Nezafat, N., Ghasemi, Y., Javadi, G., Khoshnoud, M. J. & Omidinia, E. (2014) A novel multi-epitope peptide vaccine against cancer: an in silico approach. J. Theor. Biol. 349, 121–134.
Li, M., Jiang, Y., Gong, T., Zhang, Z. & Sun, X. (2016) Intranasal Vaccination against HIV-1 with Adenoviral Vector-Based Nanocomplex Using Synthetic TLR-4 Agonist Peptide as Adjuvant. Mol. Pharm. 13, 885–894.
Chan, J., Mehta, S., Bharrhan, S., Chen, Y., Achka, J. M., Casadewall, A., Flynn, J. (2014) The role of B cells and humoral immunity in Mycobacterium tuberculosis infection. Semin. Immunol. 26, 588–600.
Busby, J. N., Panjikar, S., Landsberg, M. J., Hurs, M. R., Lott, J. S. (2013) The BC component of ABC toxins is an RHS-repeat-containing protein encapsulation device. Nature. 501: 547-550.
Rana, A. & Akhter, Y. (2016) A multi-subunit based, thermodynamically stable model vaccine using combined immunoinformatics and protein structure-based approach. Immunobiology 221, 544–557, https://doi.org/10.1016/j.imbio.2015.12.004.
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