SARS-CoV-2 receptor binding mutations and antibody mediated immunity

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Abstract

SARS-CoV-2 mutations can impact infectivity, viral load, and overall morbidity/mortality during infection. In this analysis, we look at the mutational landscape of the SARS-CoV-2 receptor binding domain, a structure that is antigenic and allows for viral binding to the host. We analyze 104193 GISAID sequences acquired on October 15 th , 2020 with a majority of sequences (96%) containing point mutations. We report high frequency mutations with improved binding affinity to ACE2 including S477N, N439K, V367F, and N501Y and address the potential impact of RBD mutations on antibody binding. The high frequency S477N mutation is present in 6.7% of all SARS-CoV-2 sequences, co-occurs with D614G, and is currently present in 14 countries. To address RBD-antibody interactions we take a subset of human derived antibodies and define their interacting residues using PDBsum. Our analysis shows that adaptive immunity against SARS-CoV-2 enlists broad coverage of the RBD suggesting that antibody mediated immunity should be sufficient to resolve infection in the presence of RBD point mutations that conserve structure.

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  1. SciScore for 10.1101/2021.01.25.427846: (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
    Specifically, antibodies B38 (PDB: 7BZ5), CV30 (PDB: 6XE1), CB6 (PDB: 7C01), BD23 (PDB: 7BYR), COVA2-39 (PDB: 7JMP), CV07-250 (PDB: 6XKQ), P2B-2F6 (PDB: 7BWJ), CV07-270 (PDB: 6XKP), BD-368-2 (PDB: 7CHE), and S309 (PDB: 6WPS).
    CV30
    suggested: None
    CB6
    suggested: None
    BD23
    suggested: None
    Software and Algorithms
    SentencesResources
    The algorithm executes local alignment in parallel using the MATLAB bioinformatics toolbox51.
    MATLAB
    suggested: (MATLAB, RRID:SCR_001622)
    Antibody Interacting Residues: The PDBsum server was used to obtain interacting residues on the protein-protein interface between antibodies and the RBD of SARS-CoV-253.
    PDBsum
    suggested: (PDBsum, RRID:SCR_006511)

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

    About SciScore

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