A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein

Nat Commun. 2021 Jan 12;12(1):288. doi: 10.1038/s41467-020-20602-5.


Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / chemistry
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology*
  • Antibodies, Viral / immunology
  • COVID-19 Drug Treatment*
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Female
  • Ferrets
  • Humans
  • Leukocytes, Mononuclear
  • Macaca mulatta
  • Male
  • Mesocricetus
  • Models, Molecular
  • Protein Binding / drug effects*
  • Protein Conformation
  • SARS-CoV-2 / drug effects*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / drug effects*
  • Vero Cells


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2