Abstract

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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)TrimerCoronavirus disease 2019 (COVID-19)Betacoronavirus2019-20 coronavirus outbreakPandemicMonoclonal antibodyVirologyAntibodyOutbreakBinding siteChemistryComputational biologyBiologyMedicineImmunologyBiochemistryDimer

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Year
2020
Type
preprint
Citations
1003
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Closed

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Kizzmekia S. Corbett, Jory A. Goldsmith, Ching‐Lin Hsieh et al. (2020). Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. bioRxiv (Cold Spring Harbor Laboratory) . https://doi.org/10.1101/2020.02.11.944462

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DOI
10.1101/2020.02.11.944462