A highly potent antibody effective against SARS-CoV-2 variants of concern

Cell Rep. 2021 Oct 12;37(2):109814. doi: 10.1016/j.celrep.2021.109814. Epub 2021 Sep 21.


Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals.

Keywords: SARS-CoV-2; neutralizing antibodies; variants of concern.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • B-Lymphocytes / immunology
  • Broadly Neutralizing Antibodies / immunology
  • Broadly Neutralizing Antibodies / therapeutic use*
  • COVID-19 / immunology
  • COVID-19 Drug Treatment*
  • Cell Line
  • Cricetinae
  • Disease Models, Animal
  • Epitopes / immunology
  • Humans
  • Immunoglobulin Fab Fragments / immunology
  • Immunoglobulin Fab Fragments / metabolism
  • Neutralization Tests
  • Protein Binding / immunology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / pathogenicity
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / ultrastructure
  • Structure-Activity Relationship
  • Vaccination


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Broadly Neutralizing Antibodies
  • Epitopes
  • Immunoglobulin Fab Fragments
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2