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
  • 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: [email protected].
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.
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