Structural Basis of Receptor Recognition by SARS-CoV-2

Nature. 2020 May;581(7807):221-224. doi: 10.1038/s41586-020-2179-y. Epub 2020 Mar 30.

Abstract

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-191,2. A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans3,4. Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.

Publication types

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

MeSH terms

  • Animals
  • Betacoronavirus / chemistry*
  • Betacoronavirus / drug effects
  • Betacoronavirus / metabolism
  • Binding Sites
  • China / epidemiology
  • Chiroptera / virology
  • Coronavirus / chemistry
  • Coronavirus / isolation & purification
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / transmission
  • Coronavirus Infections / virology
  • Crystallization
  • Crystallography, X-Ray
  • Disease Reservoirs / virology
  • Eutheria / virology
  • Humans
  • Models, Molecular
  • Pandemics
  • Peptidyl-Dipeptidase A / chemistry*
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / transmission
  • Pneumonia, Viral / virology
  • Protein Binding
  • Protein Domains
  • Protein Stability
  • Receptors, Virus / chemistry*
  • Receptors, Virus / metabolism*
  • SARS Virus / chemistry
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Zoonoses / epidemiology
  • Zoonoses / transmission
  • Zoonoses / virology*

Substances

  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2