Identification of SARS-CoV RBD-targeting monoclonal antibodies with cross-reactive or neutralizing activity against SARS-CoV-2

Antiviral Res. 2020 Jul:179:104820. doi: 10.1016/j.antiviral.2020.104820. Epub 2020 May 13.

Abstract

SARS-CoV-2-caused COVID-19 cases are growing globally, calling for developing effective therapeutics to control the current pandemic. SARS-CoV-2 and SARS-CoV recognize angiotensin-converting enzyme 2 (ACE2) receptor via the receptor-binding domain (RBD). Here, we identified six SARS-CoV RBD-specific neutralizing monoclonal antibodies (nAbs) that cross-reacted with SARS-CoV-2 RBD, two of which, 18F3 and 7B11, neutralized SARS-CoV-2 infection. 18F3 recognized conserved epitopes on SARS-CoV and SARS-CoV-2 RBDs, whereas 7B11 recognized epitopes on SARS-CoV RBD not fully conserved in SARS-CoV-2 RBD. The 18F3-recognizing epitopes on RBD did not overlap with the ACE2-binding sites, whereas those recognized by 7B11 were close to the ACE2-binding sites, explaining why 7B11 could, but 18F3 could not, block SARS-CoV or SARS-CoV-2 RBD binding to ACE2 receptor. Our study provides an alternative approach to prevent SARS-CoV-2 infection using anti-SARS-CoV nAbs.

Keywords: COVID-19; Cross-neutralization; Neutralizing monoclonal antibodies; Receptor-binding domain; SARS-CoV; SARS-CoV-2.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology
  • Antigens, Viral / chemistry
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Betacoronavirus / genetics
  • Betacoronavirus / immunology*
  • Binding Sites
  • COVID-19
  • Coronavirus Infections / virology*
  • Cross Reactions
  • Epitopes / immunology
  • HEK293 Cells
  • Humans
  • Neutralization Tests
  • Pandemics
  • Peptidyl-Dipeptidase A / immunology
  • Pneumonia, Viral / virology*
  • SARS-CoV-2
  • Severe acute respiratory syndrome-related coronavirus / genetics
  • Severe acute respiratory syndrome-related coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Epitopes
  • Spike Glycoprotein, Coronavirus
  • spike glycoprotein, SARS-CoV
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2