Bioinformatics analysis of SARS-CoV-2 RBD mutant variants and insights into antibody and ACE2 receptor binding

  1. Prashant Ranjan
  2. Neha
  3. Chandra Devi
  4. Parimal Das

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Abstract

Prevailing COVID-19 vaccines are based on the spike protein of earlier SARS-CoV-2 strain that emerged in Wuhan, China. The continuously evolving nature of SARS-CoV-2 resulting emergence of new variants raises the risk of immune absconds. During the last few months, several RBD (receptor-binding domain) variants have been reported to affect the vaccine efficacy considerably. Soon after reporting of a new double mutant variant (L452R & E484Q) in India, the country facing a deadlier second wave of infections which prompts researchers to suspects this variant to be accountable. To address the relevant concerns about this new variant affecting vaccine efficacy, we performed molecular simulation dynamics based structural analysis of spike protein of double mutant (L452R & E484Q) along with K417G variants and earlier reported RBD variants and found structural changes in RBD region after comparing with the wild type. Comparison of the binding affinity of the double mutant and earlier reported RBD variant for ACE2 (angiotensin 2 altered enzymes) receptor and CR3022 antibody with the wild-type strain revealed the lowest binding affinity of the double mutant for CR3022 among all other variants. These findings suggest that the newly emerged double mutant could significantly reduce the impact of the current vaccine which threatens the protective efficacy of current vaccine therapy.

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  1. Version published to 10.1101/2021.04.03.438113v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.04.03.438113: (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
    Retrieval of crystal structures: Crystal structures of spike protein (PDBID-7AD1), ACE2 (PDBID-6ACG) and antibody CR3022 (PDBID 6YLA) were retrieved from PDB RCSB (https://www.rcsb.org/).
    PDBID-6ACG
    suggested: None
    Protein-protein and antibody-protein interactions were visualized by LigPlot plus v2.2.
    Protein-protein
    suggested: None
    antibody-protein
    suggested: None
    Molecular interactions of antibody CR3022 and ACE2 receptor with RBD variants were performed by antibody script under antibody loop numbering scheme i.e. KABAT Scheme and DIMPLOT script algorithm package built into LigPlot plus v2.2 respectively.
    ACE2
    suggested: None
    It was found that seven structurally changed variants (F486L, Q493N, Indian double mutant (L452R & E484Q), R408I, L455Y, K417G and E484K) have high docking score against ACE2 receptor compared with wild type and less docking score against antibody (CR3022) unlike wild type (Table2).
    E484K
    suggested: None
    antibody (CR3022
    suggested: None
    Table2
    suggested: None
    Software and Algorithms
    SentencesResources
    Docking analysis: Docking of RBD mutant variants with selected targets (ACE2 receptor and antibody structure CR3022) was carried out by PatchDock server (Ranjan et al. 2020) by choosing parameter RMSD esteem 4.0 and complex type as default.
    PatchDock
    suggested: None

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2021.04.03.438113v1 on bioRxiv