A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV

Science. 2020 May 8;368(6491):630-633. doi: 10.1126/science.abb7269. Epub 2020 Apr 3.

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein at 3.1-angstrom resolution. CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBDs on the trimeric S protein are in the "up" conformation and slightly rotated. These results provide molecular insights into antibody recognition of SARS-CoV-2.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / immunology
  • Antibody Affinity
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology
  • Betacoronavirus / chemistry*
  • Betacoronavirus / immunology*
  • Binding Sites
  • Cross Reactions
  • Crystallography, X-Ray
  • Epitopes* / chemistry
  • Epitopes* / immunology
  • Models, Molecular
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / metabolism
  • Protein Conformation
  • Protein Domains
  • Protein Interaction Domains and Motifs / immunology
  • Receptors, Coronavirus
  • Receptors, Virus / chemistry
  • Receptors, Virus / metabolism
  • SARS Virus / chemistry*
  • SARS Virus / immunology*
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Epitopes
  • Receptors, Coronavirus
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike glycoprotein, SARS-CoV
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2