Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: an in silico approach

  1. M. Shaminur Rahman
  2. M. Nazmul Hoque
  3. M. Rafiul Islam
  4. Salma Akter
  5. ASM Rubayet-Ul-Alam
  6. Mohammad Anwar Siddique
  7. Otun Saha
  8. Md. Mizanur Rahaman
  9. Munawar Sultana
  10. Keith A. Crandall
  11. M. Anwar Hossain

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19), a public health emergency of international concerns declared by the World Health Organization (WHO). An immuno-informatics approach along with comparative genomics was applied to design a multi-epitope-based peptide vaccine against SARS-CoV-2 combining the antigenic epitopes of the S, M, and E proteins. The tertiary structure was predicted, refined and validated using advanced bioinformatics tools. The candidate vaccine showed an average of ≥90.0% world population coverage for different ethnic groups. Molecular docking and dynamics simulation of the chimeric vaccine with the immune receptors (TLR3 and TLR4) predicted efficient binding. Immune simulation predicted significant primary immune response with increased IgM and secondary immune response with high levels of both IgG1 and IgG2. It also increased the proliferation of T-helper cells and cytotoxic T-cells along with the increased IFN-γ and IL-2 cytokines. The codon optimization and mRNA secondary structure prediction revealed that the chimera is suitable for high-level expression and cloning. Overall, the constructed recombinant chimeric vaccine candidate demonstrated significant potential and can be considered for clinical validation to fight against this global threat, COVID-19.

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  5. Version published to 10.7717/peerj.9572
  6. ScreenIT

    SciScore for 10.1101/2020.03.30.015164: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    Since the S glycoprotein of coronaviruses is important for viral attachment to host cell, antibody against this protein acts as inhibitor30, therefore, S proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were structurally compared using SWISS homology modeling46 based on the protein databank (PDB) templates 6acd, 5w9h and 6vsb, respectively.
    antibody against this protein acts as inhibitor30
    suggested: None
    Software and Algorithms
    SentencesResources
    We aligned these sequences through MAFFT online server
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    (https://mafft.cbrc.jp/alignment/server/) using default parameters, and Wu-Kabat protein variability was analyzed in Protein variability server (http://imed.med.ucm.es/PVS/) with respect to NCBI (National Center for Biotechnology Information, https://www.ncbi.nlm.nih.gov/protein) reference genome (Accession no : NC_045512.2).
    https://www.ncbi.nlm.nih.gov/protein
    suggested: (Protein Database, RRID:SCR_017486)
    Moreover, two reference genome sequences of SARS-CoV (NC_004718.3) and MERS-CoV (NC_019843.3) were also retrieved from the NCBI database to reveal the structural heterogeneity of S protein.
    NCBI
    suggested: (NCBI, RRID:SCR_006472)
    Antigenicity of full-length S (spike glycoprotein), M (membrane protein) and E (envelope protein) proteins was predicted using VaxiJen v2.0 (http://www.ddg-pharmfac.net/vaxijen/VaxiJen/VaxiJen.html)52.
    VaxiJen
    suggested: (VaxiJen, RRID:SCR_018514)
    We used OmicsCircos to visualize the association between world population and different ethnic groups58.
    OmicsCircos
    suggested: None
    The GalaxyRefine server was further used to improving the best local structural quality of the CoV-RMEN according to the CASP10 assessment, and ProSA-web (https://prosa.services.came.sbg.ac.at/prosa.php) was used to calculate overall quality score for a specific input structure, and this is displayed in the context of all known protein structures.
    GalaxyRefine
    suggested: (GalaxyRefine, RRID:SCR_018531)
    A Ramachandran plot was obtained through the RAMPAGE server (http://mordred.bioc.cam.ac.uk/~rapper/rampage.php).
    RAMPAGE
    suggested: (RAMPAGE, RRID:SCR_017590)
    Finally, the sequence of the recombinant plasmid was designed by inserting the adapted codon sequences into pETite vector using SnapGene software (from Insightful Science; available at snapgene.com).
    SnapGene
    suggested: (SnapGene, RRID:SCR_015052)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 42, 43, 46, 47, 49, 53, 56 and 57. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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  7. Version published to 10.1101/2020.03.30.015164v1 on bioRxiv