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

Highlights

SARS-CoV-2 uses ACE2 to enter target cells

SARS-CoV-2 and SARS-CoV bind with similar affinities to ACE2

Structures of SARS-CoV-2 spike glycoprotein in two conformations

SARS-CoV polyclonal antibodies inhibit SARS-CoV-2 spike-mediated entry into cells

Summary

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.

 

Author: Alexandra C.Walls, Young-Jun Park, M. AlejandraTortorici, et al.
Link: https://is.gd/m95y51