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ISSN (Print): 2211-5501
ISSN (Online): 2211-551X

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Research Article

Design of a Multi-epitope Vaccine against Covid-19: An In silico Approach

Author(s): Kaushal Kishor Mishra, Asheesh Kumar Mishra, Vandita Anand, Anjana Pandey, Savita Budhwar and Deepak Chand Sharma*

Volume 12, Issue 3, 2023

Published on: 23 June, 2023

Page: [151 - 168] Pages: 18

DOI: 10.2174/2211550112666230612153430

Price: $65

Abstract

Background: The control of the Covid-19 epidemic depends on designing a novel, effective vaccine against it. Currently, available vaccines cannot provide complete protection against various mutants of Covid-19.

Objective: The present investigation aimed to design a new multi-epitope vaccine by using in silico tools.

Methods: In the present study, the spike-glycoprotein was targeted, desirably stimulating both B and T-cell lymphocytes, providing effective and safe responses in the host immune system. The desired vaccine has been found to possess 448 amino acids of spike glycoprotein. The prognosticated epitopes included 10 CTL, 4 linear B-cells, and 14 HTL, including the 128 amino acid sequence of 50S ribosomal protein adjuvant joined by GPGPG and AAY linkers on the N terminus of linear Bcell, HTL, and CTL epitopes, and the C-terminal joined with HHHHHH (6HIS) linker, indicating stability for vaccine structure.

Results: The molecular docking has revealed the protein-protein restricting communication between the immunization construct and the TLR-3-resistant receptor. The vaccine has been developed through selected epitopes, an adjuvant, and an additional epitope. Docking assays with toll-like receptor 3 have been run on a three-dimensional structural model of the vaccine to gauge its immunological potency. Our findings support the hypothesis that our vaccination will activate TLRmediated downstream immune pathways by aggressively interacting with the innate receptor.

Conclusion: The results suggest that the proposed chimeric peptide could initiate an efficient and safe immune response against Covid-19. The proposed vaccine has been proven safe in all critical parameters.

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[1]
Chakraborty C, Sharma A. The 2019 novel coronavirus disease (COVID-19) pandemic: A zoonotic prospective. Asian Pac J Trop Med 2020; 13: 242.
[http://dx.doi.org/10.4103/1995-7645.281613]
[2]
Chen HZ, Tang LL. Bioinformatics analysis of epitope-based vaccine design against the novel SARS-CoV-2. Infect Dis Poverty 2020; 9: 1.
[http://dx.doi.org/10.1186/s40249-020-00713-3]
[3]
WHO Statement regarding cluster of pneumonia cases in Wuhan. Available from: https://www.who.int/china/news/detail/09-01-2020-who-statement-regarding-cluster-of-pneumonia-cases-in-wuhan-china
[4]
Loyd JE, Denny JC. Coronavirus NL63-induced adult respiratory distress syndrome. Am J Respir Crit Care Med 2016; 193: 1-2.
[http://dx.doi.org/10.1164/rccm.201506-1239LE]
[5]
Weekly epidemiological update on COVID-19. 2021. Available from: Weekly epidemiological update on COVID-19
[6]
2021. Available from: https://cdn.who.int/media/docs/default-source/wrindia/situation-report/india-situation-report-86.pdf?sfvrsn=cedc203e
[7]
Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 2020; 109: 102433.
[http://dx.doi.org/10.1016/j.jaut.2020.102433]
[8]
Chen H, Guo J. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet 2020; 395: 809-15.
[http://dx.doi.org/10.1016/S0140-6736(20)30360-3]
[9]
Grifoni A, Weiskopf D. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 2020; 181: 1489-501.
[http://dx.doi.org/10.1016/j.cell.2020.05.015]
[10]
Heinz FX, Stiasny K. Distinguishing features of current COVID-19 vaccines: Knowns and unknowns of antigen presentation and modes of action. Vaccines 2021; 6: 1-13.
[http://dx.doi.org/10.1038/s41541-021-00369-6]
[11]
Sarma P, Shekhar N. In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain). J Biomol Struct Dyn 2021; 39: 2724-32.
[http://dx.doi.org/10.1080/07391102.2020.1753580]
[12]
Kumar N, Kanchan T. Update on the target structures of SARS-CoV-2: A systematic review. Indian J Pharmacol 2018; 49: 344-7.
[http://dx.doi.org/10.4103/ijp.IJP]
[13]
Khan SA, Zia K. Identification of chymotrypsin-like protease inhibitors of SARS-CoV-2 via integrated computational approach. J Biomol Struct Dyn 2021; 39: 2607-16.
[http://dx.doi.org/10.1080/07391102.2020.1751298]
[14]
Khan RJ, Jha RK. Targeting SARS-CoV-2: A systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2′-O-ribose methyltransferase. J Biomol Struct Dyn 2021; 39: 2679-92.
[http://dx.doi.org/10.1080/07391102.2020.1753577]
[15]
Hoffmann M, Kleine-Weber H. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: 271-80.
[http://dx.doi.org/10.1016/j.cell.2020.02.052]
[16]
Boopathi S, Poma AB. Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn 2020; 0: 1-10.
[http://dx.doi.org/10.1080/07391102.2020.1758788]
[17]
Enmozhi SK, Raja K. Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: An in silico approach. J Biomol Struct Dyn 2020; 0: 1-7.
[http://dx.doi.org/10.1080/07391102.2020.1760136]
[18]
Verdecchia P, Cavallini C. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med 2020; 76: 14-20.
[http://dx.doi.org/10.1016/j.ejim.2020.04.037]
[19]
Weiss SR, Navas-Martin S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev 2005; 69: 635-64.
[http://dx.doi.org/10.1128/MMBR.69.4.635-664.2005]
[20]
van de Veerdonk F, Netea MG. Kinins and Cytokines in COVID-19: A comprehensive pathophysiological approach. Preprints 2020.
[http://dx.doi.org/10.20944/preprints202004.0023.v1]
[21]
Sinha SK, Shakya A. An in-silico evaluation of different saikosaponins for their potency against SARS-CoV-2 using NSP15 and fusion spike glycoprotein as targets. J Biomol Struct Dyn 2021; 39: 3244-55.
[http://dx.doi.org/10.1080/07391102.2020.1762741]
[22]
Larsen MV, Lundegaard C. Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinformat 2007; 8: 1-12.
[http://dx.doi.org/10.1186/1471-2105-8-424]
[23]
Enayatkhani M, Hasaniazad M. Reverse vaccinology approach to design a novel multi-epitope vaccine candidate against COVID-19: An in silico study. J Biomol Struct Dyn 2021; 39: 2857-72.
[http://dx.doi.org/10.1080/07391102.2020.1756411]
[24]
Peele KA, Srihansa T. Design of multi-epitope vaccine candidate against SARS-CoV-2: a in-silico study Design of multi-epitope vaccine candidate against SARS-CoV-2: A in-silico study. J Biomol Struct Dyn 2020; 0: 1-9.
[http://dx.doi.org/10.1080/07391102.2020.1770127]
[25]
Dey S, De A. Rational design of peptide vaccines against multiple types of human papillomavirus. Cancer Inform 2016; 15: 1-16.
[http://dx.doi.org/10.4137/CIN.S39071]
[26]
Vankadari N, Wilce A. Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg Microbes Infect 2020; 9: 601-4.
[http://dx.doi.org/10.1080/22221751.2020.1739565]
[27]
Sarkar T, Das S. H7N9 Influenza Outbreak in China 2013: In silico analyses of conserved segments of the hemagglutinin as a basis for the selection of peptide vaccine targets. Comput Biol Chem 2015; 59: 8-15.
[http://dx.doi.org/10.1016/j.compbiolchem.2015.08.003]
[28]
Yang Y, Zhang L. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein Cell 2013; 4: 951-61.
[http://dx.doi.org/10.1007/s13238-013-3096-8]
[29]
Gálve J, Zanni R. Drugs repurposing for coronavirus treatment: Computational study based on molecular topology. Nereis 2020; 12: 15-8.
[http://dx.doi.org/10.46583/nereis_2020.12.591]
[30]
Nandy A, Dey S. Epidemics and peptide vaccine response-a brief review. Curr Top Med Chem 2018; 118: 2202-8.
[http://dx.doi.org/10.2174/1568026618666181112144745]
[31]
Elfiky AA, Azzam EB. Novel guanosine derivatives against MERS-CoV polymerase: An in silico perspective. J Biomol Struct Dyn 2021; 39: 2923-31.
[http://dx.doi.org/10.1080/07391102.2020.1758789]
[32]
Simmons G, Zmora P. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. Antiviral Res 2013; 100: 605-14.
[http://dx.doi.org/10.1016/j.antiviral.2013.09.028]
[33]
Review-CDC Online Newsroom-CDC. 2021.
[34]
Peters B, Sidney J, Bourne P, Bui H-H, Buus S. The immune epitope database and analysis resource: from vision to blueprint. PLoS Biol 2005; 3(3): e91.
[http://dx.doi.org/10.1371/journal.pbio.0030091]
[35]
Binkowski TA, Naghibzadeh S. CASTp: Computed atlas of surface topography of proteins. Nucleic Acids Res 2003; 31: 3352-5.
[http://dx.doi.org/10.1093/nar/gkg512]
[36]
Ichiye T, Karplus M. Collective motions in proteins: A covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations. Proteins 1991; 11: 205-17.
[http://dx.doi.org/10.1002/prot.340110305]
[37]
Rapin N, Lund O. Computational immunology meets bioinformatics: the use of prediction tools for molecular binding in the simulation of the immune system. PLoS One 2010; 5: 1-14.
[http://dx.doi.org/10.1371/journal.pone.0009862]
[38]
Robinson J, Guethlein LA. Distinguishing functional polymorphism from random variation in the sequences of >10,000 HLA-A, -B and -C alleles. PLoS Genet 2017; 13: 1-28.
[http://dx.doi.org/10.1371/journal.pgen.1006862]
[39]
Koretzky GA. Multiple roles of CD4 and CD8 in T cell activation. J Immunol 2010; 185: 2643-4.
[http://dx.doi.org/10.4049/jimmunol.1090076]
[40]
Reche P, Flower DR. Peptide-based immunotherapeutics and vaccines 2015. J Immunol Res 2015; 2015: 349049.
[http://dx.doi.org/10.1155/2015/349049]
[41]
Naz A, Awan FM. Identification of putative vaccine candidates against Helicobacter pylori exploiting exoproteome and secretome: A reverse vaccinology based approach. Infect Genet Evol 2015; 32: 280-91.
[http://dx.doi.org/10.1016/j.meegid.2015.03.027]
[42]
Cao W-C, Liu W. Disappearance of antibodies to SARS-Associated coronavirus after recovery. N Engl J Med 2007; 357: 1162-3.
[http://dx.doi.org/10.1056/NEJMc070348]
[43]
Ni L, Ye F. Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals. Immunity 2020; 52: 971-7.
[http://dx.doi.org/10.1016/j.immuni.2020.04.023]
[44]
Dar HA, Zaheer T. Immunoinformatics-aided design and evaluation of a potential multi-epitope vaccine against klebsiella pneumoniae. Vaccines 2019; 7: 1-17.
[http://dx.doi.org/10.3390/vaccines7030088]
[45]
Liu H, Irvine DJ. Guiding principles in the design of molecular bioconjugates for vaccine applications. Bioconjug Chem 2015; 26: 791-801.
[http://dx.doi.org/10.1021/acs.bioconjchem.5b00103]
[46]
López-Blanc JR, Aliaga JI. iMODS: internal coordinates normal mode analysis server. Nucleic Acids Res 2014; 42: 271-6.
[http://dx.doi.org/10.1093/nar/gku339]
[47]
Zhou P, Yang XL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579: 270-3.
[http://dx.doi.org/10.1038/s41586-020-2012-7]
[48]
Zhu N, Zhang D. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382: 727-33.
[http://dx.doi.org/10.1056/NEJMoa2001017]
[49]
Zumla J, Chan JFW. Coronaviruses-drug discovery and therapeutic options. Nat Rev Drug Discov 2016; 15: 327-47.
[http://dx.doi.org/10.1038/nrd.2015.37]
[50]
Kar TN, Basak U. A candidate multi-epitope vaccine against SARS-CoV-2. Sci Rep 2020; 10.
[http://dx.doi.org/10.1038/s41598-020-67749-1] [PMID: 32616763]
[51]
Ceraolo C, Giorgi FM. Genomic variance of the 2019-nCoV coronavirus. J Med Virol 2020; 92: 522-8.
[http://dx.doi.org/10.1002/jmv.25700]

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