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 coronavirus (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 vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo–electron microscopy 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 provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures 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).

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  2. Version published to 10.1126/science.abb2507
  3. Version published to 10.1101/2020.02.11.944462v1 on bioRxiv