Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Cell. 2020 Apr 16;181(2):281-292.e6. doi: 10.1016/j.cell.2020.02.058. Epub 2020 Mar 9.

Abstract

The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

Keywords: SARS-CoV; SARS-CoV-2; antibodies; coronavirus; cryo-EM; neutralizing antibodies; spike glycoprotein; viral receptor.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Neutralizing / metabolism
  • Antibodies, Neutralizing / pharmacology
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology
  • Antigens, Viral / metabolism
  • Betacoronavirus / chemistry
  • Betacoronavirus / metabolism*
  • Cell Line
  • Cryoelectron Microscopy
  • Humans
  • Models, Molecular
  • Peptidyl-Dipeptidase A / metabolism
  • Receptors, Virus / chemistry
  • Receptors, Virus / metabolism
  • SARS Virus / metabolism
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Spike Glycoprotein, Coronavirus / ultrastructure*
  • Virus Internalization / drug effects

Substances

  • Antibodies, Neutralizing
  • Antigens, Viral
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2

Supplementary concepts

  • severe acute respiratory syndrome coronavirus 2