Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Science. 2020 Mar 13;367(6483):1260-1263. doi: 10.1126/science.abb2507. Epub 2020 Feb 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Antibodies, Monoclonal / immunology
  • Antibodies, Viral / immunology
  • Betacoronavirus / chemistry*
  • Betacoronavirus / immunology
  • Betacoronavirus / metabolism
  • Betacoronavirus / ultrastructure
  • Cross Reactions
  • Cryoelectron Microscopy
  • Image Processing, Computer-Assisted
  • Models, Molecular
  • Peptidyl-Dipeptidase A / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Protein Multimerization
  • Receptors, Coronavirus
  • Receptors, Virus / metabolism
  • SARS-CoV-2
  • Severe acute respiratory syndrome-related coronavirus / chemistry
  • Severe acute respiratory syndrome-related coronavirus / immunology
  • Severe acute respiratory syndrome-related coronavirus / ultrastructure
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Spike Glycoprotein, Coronavirus / ultrastructure*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Receptors, Coronavirus
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2