2. Academic Validation
  3. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

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.
Alexandra C Walls 1,  Young-Jun Park 1,  M Alejandra Tortorici 2,  Abigail Wall 3,  Andrew T McGuire 4,  David Veesler 5
Affiliations

Affiliations

  • 1 Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • 2 Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute Pasteur & CNRS UMR 3569, Unité de Virologie Structurale, Paris 75015, France.
  • 3 Vaccines and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA.
  • 4 Vaccines and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
  • 5 Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address: dveesler@uw.edu.
PMID: 32155444 DOI: 10.1016/j.cell.2020.02.058
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.

Figures
Products