The influence of major S protein mutations of SARS-CoV-2 on the potential B cell epitopes

  1. Xianlin Yuan
  2. liangping li

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Abstract

SARS-CoV-2 has rapidly transmitted worldwide and results in the COVID-19 pandemic. Spike glycoprotein on surface is a key factor of viral transmission, and has appeared a lot of variants due to gene mutations, which may influence the viral antigenicity and vaccine efficacy. Here, we used bioinformatic tools to analyze B-cell epitopes of prototype S protein and its 9 common variants. 12 potential linear and 53 discontinuous epitopes of B-cells were predicted from the S protein prototype. Importantly, by comparing the epitope alterations between prototype and variants, we demonstrate that B-cell epitopes and antigenicity of 9 variants appear significantly different alterations. The dominant D614G variant impacts the potential epitope least, only with moderately elevated antigenicity, while the epitopes and antigenicity of some mutants(V483A, V367F, etc.) with small incidence in the population change greatly. These results suggest that the currently developed vaccines should be valid for a majority of SARS-CoV-2 infectors. This study provides a scientific basis for large-scale application of SARS-CoV-2 vaccines and for taking precautions against the probable appearance of antigen escape induced by genetic variation after vaccination.

Author Summary

The global pandemic of SARS-CoV-2 has lasted for more than half a year and has not yet been contained. Until now there is no effective treatment for SARS-CoV-2 caused disease (COVID-19). Successful vaccine development seems to be the only hope. However, this novel coronavirus belongs to the RNA virus, there is a high mutation rate in the genome, and these mutations often locate on the Spike proteins of virus, the gripper of the virus entering the cells. Vaccination induce the generation of antibodies, which block Spike protein. However, the Spike protein variants may change the recognition and binding of antibodies and make the vaccine ineffective. In this study, we predict neutralizing antibody recognition sites (B cell epitopes) of the prototype S protein of SARS-COV2, along with several common variants using bioinformatics tools. We discovered the variability in antigenicity among the mutants, for instance, in the more widespread D614G variant the change of epitope was least affected, only with slight increase of antigenicity. However, the antigenic epitopes of some mutants change greatly. These results could be of potential importance for future vaccine design and application against SARS-CoV2 variants.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.24.264895: (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

    Software and Algorithms
    SentencesResources
    By utilizing Clustal Omega tool (Version 1.2.4) [27] and MSAViewer tool from VIPR database (https://www.viprbrc.org), multiple sequence alignment (MSA) was carried out to perceive the conservation of sequence twice [28].
    Clustal Omega tool
    suggested: None
    VIPR
    suggested: (vipR, RRID:SCR_010685)
    The aligned files were additionally applied to make phylogenetic tree via Clustal Omega Self-contained analytical tools (https://www.ebi.ac.uk/Tools).
    Clustal Omega
    suggested: (Clustal Omega, RRID:SCR_001591)
    The Conserved Domain Database (CDD) tool [29] in the NCBI website was used to analyze the main functional domains of S proteins and to determine the detail functional domains of S proteins with reference of Jun Lan’s study [13].
    NCBI
    suggested: (NCBI, RRID:SCR_006472)
    An TMHMM online tool (http://www.cbs.dtu.dk/services/TMHMM/) was used to examine the transmembrane topology of S protein [30].
    http://www.cbs.dtu.dk/services/TMHMM/
    suggested: (TMHMM Server, RRID:SCR_014935)
    We predicted the discontinuous epitopes of prototype S protein via DiscoTope 2.0 server [38] by entering PDB ID number: 6VYB.
    DiscoTope
    suggested: (DiscoTope, RRID:SCR_018530)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    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: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.08.24.264895v1 on bioRxiv