Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein

  1. Christine Toelzer
  2. Kapil Gupta
  3. Sathish K. N. Yadav
  4. Ufuk Borucu
  5. Andrew D. Davidson
  6. Maia Kavanagh Williamson
  7. Deborah K. Shoemark
  8. Frederic Garzoni
  9. Oskar Staufer
  10. Rachel Milligan
  11. Julien Capin
  12. Adrian J. Mulholland
  13. Joachim Spatz
  14. Daniel Fitzgerald
  15. Imre Berger
  16. Christiane Schaffitzel

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Abstract

Many efforts to develop therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are focused on the spike (S) protein trimer that binds to the host receptor. Structures of trimeric S protein show its receptor-binding domain in either an up or a down conformation. Toelzer et al. produced SARS-CoV-2 S in insect cells and determined the structure by cryo–electron microscopy. In their dataset, the closed form was predominant and was stabilized by binding linoleic acid, an essential fatty acid. A similar binding pocket appears to be present in previous highly pathogenic coronaviruses, and past studies suggested links between viral infection and fatty acid metabolism. The pocket could be exploited to develop inhibitors that trap S protein in the closed conformation.

Science , this issue p. 725

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    SciScore for 10.1101/2020.06.18.158584: (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

    No key resources detected.

    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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 19 and 21. 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.
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    • 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 10.1126/science.abd3255
  3. ScreenIT

    SciScore for 10.1101/2020.06.18.158584: (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
    Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix.
    Phenix
    suggested: (Phenix, SCR_014224)

    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 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 OddPub: Thank you for sharing your data.

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.06.18.158584v1 on bioRxiv