E156G and Arg158, Phe-157/del mutation in NTD of spike protein in B.1.617.2 lineage of SARS-CoV-2 leads to immune evasion through antibody escape

  1. Armi M Chaudhari
  2. Dinesh Kumar
  3. Madhvi Joshi
  4. Amrutlal Patel
  5. Chaitanya Joshi

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Abstract

Emerging variants of SARS-CoV-2 with better immune escape mechanisms and higher transmissibility remains a persistent threat across the globe. B.1.617.2 (Delta) variant was first emerged from Maharashtra, India in December, 2020. This variant is classified to be a major cause and concern of the second wave of COVID-19 in India. In the present study, we explored the genomic and structural basis of this variant through computational analysis, protein modelling and molecular dynamics (MD) simulations approach. B.1.617.2 variant carried E156G and Arg158, Phe-157/del mutations in NTD of spike protein. These mutations in N-terminal domain (NTD) of spike protein of B.1.617.2 variant revealed more rigidity and reduced flexibility compared to spike protein of Wuhan isolate. Further, docking and MD simulation study with 4A8 monoclonal antibody which was reported to bind NTD of spike protein suggested reduced binding of B.1.617.2 spike protein compared to that of spike protein of Wuhan isolate. The results of the present study demonstrate the possible case of immune escape and thereby fitness advantage of the new variant and further warrants demonstration through experimental evidence. Our study identified the probable mechanism through which B.1.617.2 variant is more pathogenically evolved with higher transmissibility as compared to the wild-type.

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  1. Version published to 10.1101/2021.06.07.447321v3 on bioRxiv
  2. Version published to 10.1101/2021.06.07.447321v2 on bioRxiv
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    SciScore for 10.1101/2021.06.07.447321: (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
    For binding residues (as shown in figure 2A) detection among both receptor (spike) and ligand (antibody-4A8) attraction forces were applied with <3Å cut off.
    antibody-4A8
    suggested: None
    Software and Algorithms
    SentencesResources
    Mutated spike from SARS-CoV-2 used in this study were derived from amino acid sequence submitted in GAISAD with accession number EPI_ISL_2001211.
    GAISAD
    suggested: None
    Missing side chains were added through PRIME and pKa refinement was done with epik [17].
    PRIME
    suggested: (Prime, RRID:SCR_014887)
    PYMOL was used for obtaining high resolution images [24].
    PYMOL
    suggested: (PyMOL, RRID:SCR_000305)
    DCCM and PCA both were analyzed using Schrodinger 2021-1 implemented python script run trj_essential_dynamics.py script of Desmond [18].
    python
    suggested: (IPython, RRID:SCR_001658)

    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: 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.

    Results from scite Reference Check: We found no unreliable references.

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  4. Version published to 10.1101/2021.06.07.447321v1 on bioRxiv