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bioRxiv · 10.1101/2020.02.11.944462

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

Wrapp, D.·Wang, N.·Corbett, K. S.·Goldsmith, J. A.·Hsieh, C.-L.·Abiona, O.·Graham, B. S.·McLellan, J. S.
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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 [A]-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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Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., McLellan, J. S.. 2020-02-15. Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. https://doi.org/10.1101/2020.02.11.944462

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