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

Corresponding author: David Veesler

Affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute Pasteur & CNRS UMR 3569, Unite´ de Virologie Structurale, Paris 75015, France; 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.

Publication date: this article was published online on March 9, 2020

DOI: https://doi.org/10.1016/j.cell.2020.02.058

Highlights

Receptor recognition is the first step of viral infection and is a key determinant of host cell and tissue tropism. The researchers 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. They 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. They 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, they 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.

Nomination Reasons

The findings presented in this article provide a structural framework to identify conserved and accessible epitopes across S glycoproteins that will support ongoing vaccine design efforts. Besides, elicitation of diverse, polyclonal Ab responses might prove key in light of the diversity of viruses circulating in animal reservoirs and in preventing the possible emergence of viral neutralization escape mutants.

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