Glycosaminoglycans induce conformational change in the SARS-CoV-2 Spike S1 Receptor Binding Domain

  1. Courtney J. Mycroft-West
  2. Dunhao Su
  3. Yong Li
  4. Scott E. Guimond
  5. Timothy R. Rudd
  6. Stefano Elli
  7. Gavin Miller
  8. Quentin M. Nunes
  9. Patricia Procter
  10. Antonella Bisio
  11. Nicholas R. Forsyth
  12. Jeremy E. Turnbull
  13. Marco Guerrini
  14. David G. Fernig
  15. Edwin A. Yates
  16. Marcelo A. Lima
  17. Mark A. Skidmore

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Abstract

The glycosaminoglycan (GAG) class of polysaccharides are utilised by a plethora of microbial pathogens as receptors for adherence and invasion. The GAG heparin prevents infection by a range of viruses when added exogenously, including the S-associated coronavirus strain HSR1 and more recently we have demonstrated that heparin can block cellular invasion by SARS-CoV-2. Heparin has found widespread clinical use as anticoagulant drug and this molecule is routinely used as a proxy for the GAG, heparan sulphate (HS), a structural analogue located on the cell surface, which is a known receptor for viral invasion. Previous work has demonstrated that unfractionated heparin and low molecular weight heparins binds to the Spike (S1) protein receptor binding domain, inducing distinct conformational change and we have further explored the structural features of heparin with regard to these interactions. In this article, previous research is expanded to now include a broader range of GAG family members, including heparan sulphate. This research demonstrates that GAGs, other than those of heparin (or its derivatives), can also interact with the SARS-CoV-2 Spike S1 receptor binding domain and induce distinct conformational changes within this region. These findings pave the way for future research into next-generation, tailor-made, GAG-based antiviral agents, against SARS-CoV-2 and other members of the Coronaviridae .

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    SciScore for 10.1101/2020.04.29.068767: (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
    Collected data were analysed with Spectral Manager II software prior to processing with GraphPad Prism 7, using second order polynomial smoothing through 21 neighbours.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    To ensure that the CD spectral change of SARS-CoV-2 S1 RBD in the presence of GAGs did not arise from simply from the addition of the GAG spectra (this class of carbohydrates are known to possess CD spectrum at high concentrations12,13), difference spectra were analysed for each GAG in order to verify that the change in the CD spectrum arose from a conformational change following binding to the test GAG.
    GAG
    suggested: None

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.04.29.068767v1 on bioRxiv