Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

Nature. 2020 May;581(7807):215-220. doi: 10.1038/s41586-020-2180-5. Epub 2020 Mar 30.

Abstract

A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Antibodies, Neutralizing / immunology
  • Betacoronavirus / chemistry*
  • Betacoronavirus / metabolism
  • Binding Sites
  • Conserved Sequence
  • Crystallography, X-Ray
  • Epitopes / chemistry
  • Epitopes / immunology
  • Evolution, Molecular
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Peptidyl-Dipeptidase A / chemistry*
  • Peptidyl-Dipeptidase A / metabolism*
  • Protein Binding
  • Protein Domains
  • Receptors, Virus / chemistry*
  • Receptors, Virus / metabolism*
  • SARS Virus / chemistry
  • SARS-CoV-2
  • Salts / chemistry
  • Sequence Alignment
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Water / analysis
  • Water / chemistry

Substances

  • Antibodies, Neutralizing
  • Epitopes
  • Receptors, Virus
  • Salts
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Water
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2