Characterization of the Receptor-Binding Domain (RBD) of 2019 Novel Coronavirus: Implication for Development of RBD Protein as a Viral Attachment Inhibitor and Vaccine

Cell Mol Immunol. 2020 Jun;17(6):613-620. doi: 10.1038/s41423-020-0400-4. Epub 2020 Mar 19.

Abstract

The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross-react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.

Keywords: 2019 novel coronavirus; SARS-CoV-2; cross-neutralization; receptor-binding domain; spike protein; viral inhibitor.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / immunology
  • Betacoronavirus / immunology
  • Betacoronavirus / metabolism*
  • Binding Sites
  • Chiroptera
  • Coronavirus Infections / immunology
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / prevention & control
  • Coronavirus Infections / therapy
  • Coronavirus Infections / virology*
  • Cross Reactions
  • HEK293 Cells
  • Humans
  • Mice
  • Pandemics
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / therapy
  • Pneumonia, Viral / virology*
  • Protein Binding
  • Receptor, Angiotensin, Type 2 / metabolism*
  • SARS Virus / immunology
  • SARS Virus / metabolism
  • Sequence Alignment
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Viral Vaccines* / immunology
  • Viral Vaccines* / metabolism
  • Virus Internalization

Substances

  • Antibodies, Viral
  • COVID-19 vaccine
  • Receptor, Angiotensin, Type 2
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • spike protein, SARS-CoV-2

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2