Structural basis for cell-type specific evolution of viral fitness by SARS-CoV-2

  1. Kapil Gupta
  2. Christine Toelzer
  3. Maia Kavanagh Williamson
  4. Deborah K. Shoemark
  5. A. Sofia F. Oliveira
  6. David A. Matthews
  7. Abdulaziz Almuqrin
  8. Oskar Staufer
  9. Sathish K.N. Yadav
  10. Ufuk Borucu
  11. Frederic Garzoni
  12. Daniel Fitzgerald
  13. Joachim Spatz
  14. Adrian J. Mulholland
  15. Andrew D. Davidson
  16. Christiane Schaffitzel
  17. Imre Berger

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Abstract

As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants which is of particular concern due to their potential for increased transmissibility and pathology. In addition to this entrenched variant diversity in circulation, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation by passaging SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike glycoprotein an eight amino-acid deletion encompassing the furin recognition motif and S1/S2 cleavage site. Here, we elucidate the structure, function and molecular dynamics of this variant spike providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity of this SARS-CoV-2 variant. Moreover, our study reveals long-range allosteric communication between functional regions within the spike that differ in wild-type and deletion variant. Our results support a view of SARS-CoV-2 probing multiple evolutionary trajectories in distinct cell types within the same infected host.

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  1. Version published to 10.1101/2021.05.11.443384v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.05.11.443384: (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

    Software and Algorithms
    SentencesResources
    Cryo-EM data processing: The dose-fractionated movies were gain-normalized, aligned, and dose-weighted using MotionCor2 (45).
    MotionCor2
    suggested: (MotionCor2, RRID:SCR_016499)
    Local resolution maps were generated using Relion 3.1 (fig.
    Relion
    suggested: (RELION, RRID:SCR_016274)
    Namdinator (51) and Coot were used to improve the fit and N-linked glycans were built into the density for both models where visible.
    Coot
    suggested: (Coot, RRID:SCR_014222)
    The model for C1 and C3-symmetrized closed conformation was real space refined with Phenix (53), and the quality was additionally analyzed using MolProbity (54) and EMRinger (55), to validate the stereochemistry of the components.
    Phenix
    suggested: (Phenix, RRID:SCR_014224)
    MolProbity
    suggested: (MolProbity, RRID:SCR_014226)
    Figures were prepared using UCSF chimera and PyMOL (Schrodinger, Inc)
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)
    The data was plotted using Microsoft excel.
    Microsoft excel
    suggested: (Microsoft Excel, RRID:SCR_016137)

    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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

    About SciScore

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  3. Version published to 10.1101/2021.05.11.443384v1 on bioRxiv