E484K and N501Y SARS-CoV 2 spike mutants Increase ACE2 recognition but reduce affinity for neutralizing antibody

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Abstract

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  1. SciScore for 10.1101/2021.06.23.449627: (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
    Preparation of spike mutants, spike-ACE2, and spike-antibody complexes: Recently, I refined the crystal structure of the SARS-CoV2 RBD-ACE2 complex (PDB ID: 6M0J19) using extensive molecular dynamics simulation, which was used as a starting structure for the present study.
    spike-ACE2
    suggested: None
    The recently resolved crystal structure of the SARS-CoV2 spike RBD complexed with a neutralizing antibody (B38) was considered for the study (PDB ID:7BZ5).
    B38
    suggested: None
    Calculation of the potential of mean force (PMF) for wild-type and mutant spike RBD to ACE2 and B38 antibody: The optimized wild-type and mutant (E484K and N501Y) SARS-CoV2 RBD complexed with ACE2 and B38 were immersed in a triclinic box filled with TIP3P water such that the minimum distance between any protein atom and box edges was > 10 ◻.
    ACE2
    suggested: None
    Software and Algorithms
    SentencesResources
    Equilibrium simulations of wild-type and mutant SARS-CoV2 spike RBD-ACE2 and RBD-antibody complexes: All the simulations were performed using GROMACS 2018.122,23 packages using the AMBER99SB-ILDN force field.
    GROMACS
    suggested: (GROMACS, RRID:SCR_014565)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 22. 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.
    • 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.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.