Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation

  1. Daniel Wrapp
  2. Nianshuang Wang
  3. Kizzmekia S. Corbett
  4. Jory A. Goldsmith
  5. Ching-Lin Hsieh
  6. Olubukola Abiona
  7. Barney S. Graham
  8. Jason S. McLellan

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Abstract

The outbreak of a novel betacoronavirus (2019-nCov) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for urgently needed vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure (MCM) development we determined a 3.5 Å-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than SARS-CoV S. Additionally we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to nCoV-2019 S, suggesting antibody cross-reactivity may be limited between the two virus RBDs. The atomic-resolution structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.

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    SciScore for 10.1101/2020.02.11.944462: (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

    Antibodies
    SentencesResources
    Due to the indispensable function of the S protein it represents a vulnerable target for antibody-mediated neutralization , and characterization of the prefusion S structure would provide atomic-level information to guide vaccine design and development .
    antibody-mediated neutralization ,
    suggested: None
    , e1007236 ( 2018) . W . C . Hwang et al. , Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody , 80R .
    anti-severe acute respiratory syndrome spike protein
    suggested: None
    Software and Algorithms
    SentencesResources
    Models were built in Coot , before being iteratively refined in both Phenix and ISOLDE ( 34-36) .
    Coot
    suggested: (Coot, SCR_014222)
          <div style="margin-bottom:8px">
        <div><b>Phenix</b></div>
        <div>suggested: (Phenix, <a href="https://scicrunch.org/resources/Any/search?q=SCR_014224">SCR_014224</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">BioRXiv , ( 2020) . B . Carragher et al. , Leginon: an automated system for acquisition of images from vitreous ice specimens .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>BioRXiv</b></div>
        <div>suggested: (bioRxiv, <a href="https://scicrunch.org/resources/Any/search?q=SCR_003933">SCR_003933</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">, 33-45 ( 2000) . D . Tegunov , P . Cramer , Real-time cryo-electron microscopy data preprocessing with Warp .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Warp</b></div>
        <div>suggested: (Warp, <a href="https://scicrunch.org/resources/Any/search?q=SCR_018071">SCR_018071</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">CryoSPARC 3D variability analysis .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>CryoSPARC</b></div>
        <div>suggested: (cryoSPARC, <a href="https://scicrunch.org/resources/Any/search?q=SCR_016501">SCR_016501</a>)</div>
      </div>
    </td></tr></table>

    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).

    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.

  2. Version published to 10.1101/2020.02.11.944462 on bioRxiv