The basis of a more contagious 501Y.V1 variant of SARS-COV-2

  1. Haolin Liu
  2. Qianqian Zhang
  3. Pengcheng Wei
  4. Zhongzhou Chen
  5. Katja Aviszus
  6. John Yang
  7. Walter Downing
  8. Shelley Peterson
  9. Chengyu Jiang
  10. Bo Liang
  11. Lyndon Reynoso
  12. Gregory P. Downey
  13. Stephen K. Frankel
  14. John Kappler
  15. Philippa Marrack
  16. Gongyi Zhang

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Abstract

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing a world-wide pandemic. A variant of SARS-COV-2 (20I/501Y.V1) recently discovered in the United Kingdom has a single mutation from N501 to Y501 within the receptor binding domain (Y501-RBD), of the Spike protein of the virus. This variant is much more contagious than the original version (N501-RBD). We found that this mutated version of RBD binds to human Angiotensin Converting Enzyme 2 (ACE2) a ~10 times more tightly than the native version (N501-RBD). Modeling analysis showed that the N501Y mutation would allow a potential aromatic ring-ring interaction and an additional hydrogen bond between the RBD and ACE2. However, sera from individuals immunized with the Pfizer-BioNTech vaccine still efficiently block the binding of Y501-RBD to ACE2 though with a slight compromised manner by comparison with their ability to inhibit binding to ACE2 of N501-RBD. This may raise the concern whether therapeutic anti-RBD antibodies used to treat COVID-19 patients are still efficacious. Nevertheless, a therapeutic antibody, Bamlanivimab, still binds to the Y501-RBD as efficiently as its binds to N501-RBD.

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  1. ScreenIT

    SciScore for 10.1101/2021.02.02.428884: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The bound antibody was detected with AP conjugated goat-anti- human IgG antibody.
    human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The protein was transiently expressed in 293F cells and purified by nickel column.
    293F
    suggested: RRID:CVCL_D615)
    Software and Algorithms
    SentencesResources
    To docking RBD N501Y mutant to ACE2, the RBD amino acid at position 501 was mutant from Asparagine (N) to Tyrosine (Y) by Coot software(Emsley and Cowtan 2004b).
    Coot
    suggested: (Coot, RRID:SCR_014222)
    The structures were shown using PyMOL.
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)

    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

    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.

  2. Version published to 10.1101/2021.02.02.428884 on bioRxiv