Map of SARS-CoV-2 spike epitopes not shielded by glycans

  1. Mateusz Sikora
  2. Sören von Bülow
  3. Florian E. C. Blanc
  4. Michael Gecht
  5. Roberto Covino
  6. Gerhard Hummer

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Abstract

The severity of the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, calls for the urgent development of a vaccine. The primary immunological target is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface to mediate viral entry into the host cell. To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics in epitope mapping.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.03.186825: (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
    We performed MD simulations of the four S proteins for 1.93 μs in the NpT ensemble with GROMACS 2019.6 [25].
    GROMACS
    suggested: (GROMACS, RRID:SCR_014565)
    Sequence-based epitope predictions: We estimated the epitope probability prediction by using the BepiPred 2.0 webserver (http://www.cbs.dtu.dk/services/BepiPred/), with an Epitope Threshold of 0.5 [32]
    BepiPred
    suggested: (BepiPred-2.0, RRID:SCR_018499)
    We added missing loops using MODELLER [2].
    MODELLER
    suggested: (MODELLER, RRID:SCR_008395)
    Assembly of full-length S model: A full-length model of S was built by manually matching the separate structural domains using PyMOL [10], and then building missing connecting residues as unstructured linkers with MODELLER [2].
    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.

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  2. Version published to 10.1101/2020.07.03.186825v1 on bioRxiv