Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation
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Preprint
- 15 February 2020
- preprint
- Published by Cold Spring Harbor Laboratory in bioRxiv
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.Keywords
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- Published version: Science, 367 (6483), 1260.
This publication has 40 references indexed in Scilit:
- Collaboration gets the most out of softwareeLife, 2013
- Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune ResponseJournal of Virology, 2011
- Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sitesProceedings of the National Academy of Sciences, 2009
- Cathepsin L Functionally Cleaves the Severe Acute Respiratory Syndrome Coronavirus Class I Fusion Protein Upstream of Rather than Adjacent to the Fusion PeptideJournal of Virology, 2008
- Structural Basis of Neutralization by a Human Anti-severe Acute Respiratory Syndrome Spike Protein Antibody, 80RJournal of Biological Chemistry, 2006
- Structure of Severe Acute Respiratory Syndrome Coronavirus Receptor-binding Domain Complexed with Neutralizing AntibodyJournal of Biological Chemistry, 2006
- Coot: model-building tools for molecular graphicsActa Crystallographica Section D-Biological Crystallography, 2004
- Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirusNature, 2003
- The Coronavirus Spike Protein Is a Class I Virus Fusion Protein: Structural and Functional Characterization of the Fusion Core ComplexJournal of Virology, 2003
- Leginon: An Automated System for Acquisition of Images from Vitreous Ice SpecimensJournal of Structural Biology, 2000