Structure-based design of prefusion-stabilized SARS-CoV-2 spikes

  1. Ching-Lin Hsieh
  2. Jory A. Goldsmith
  3. Jeffrey M. Schaub
  4. Andrea M. DiVenere
  5. Hung-Che Kuo
  6. Kamyab Javanmardi
  7. Kevin C. Le
  8. Daniel Wrapp
  9. Alison G. Lee
  10. Yutong Liu
  11. Chia-Wei Chou
  12. Patrick O. Byrne
  13. Christy K. Hjorth
  14. Nicole V. Johnson
  15. John Ludes-Meyers
  16. Annalee W. Nguyen
  17. Juyeon Park
  18. Nianshuang Wang
  19. Dzifa Amengor
  20. Jason J. Lavinder
  21. Gregory C. Ippolito
  22. Jennifer A. Maynard
  23. Ilya J. Finkelstein
  24. Jason S. McLellan

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Abstract

The development of therapeutic antibodies and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on the spike (S) protein that decorates the viral surface. A version of the spike ectodomain that includes two proline substitutions (S-2P) and stabilizes the prefusion conformation has been used to determine high-resolution structures. However, even S-2P is unstable and difficult to produce in mammalian cells. Hsieh et al. characterized many individual and combined structure-guided substitutions and identified a variant, named HexaPro, that retains the prefusion conformation but shows higher expression than S-2P and can also withstand heating and freezing. This version of the protein is likely to be useful in the development of vaccines and diagnostics.

Science , this issue p. 1501

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  1. Version published to 10.1126/science.abd0826
  2. ScreenIT

    SciScore for 10.1101/2020.05.30.125484: (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.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The one-RBD-up reconstruction was subjected to local B-factor sharpening using LocalDeBlur36 and the two-RBD-up reconstruction was sharpened in cryoSPARC.
    cryoSPARC
    suggested: (cryoSPARC, RRID:SCR_016501)
    Iterative model building and refinement were performed with Coot, Phenix and ISOLDE37–39.
    Coot
    suggested: (Coot, RRID:SCR_014222)

    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 35. 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.

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  3. Version published to 10.1101/2020.05.30.125484v1 on bioRxiv