Identification of Human Single-Domain Antibodies against SARS-CoV-2

Cell Host Microbe. 2020 Jun 10;27(6):891-898.e5. doi: 10.1016/j.chom.2020.04.023. Epub 2020 May 14.


The worldwide spread of COVID-19 highlights the need for an efficient approach to rapidly develop therapeutics and prophylactics against SARS-CoV-2. The SARS-CoV-2 spike protein, containing the receptor-binding domain (RBD) and S1 subunit involved in receptor engagement, is a potential therapeutic target. We describe the development of a phage-displayed single-domain antibody library by grafting naive complementarity-determining regions (CDRs) into framework regions of a human germline immunoglobulin heavy chain variable region (IGHV) allele. Panning this library against SARS-CoV-2 RBD and S1 subunit identified fully human single-domain antibodies targeting five distinct epitopes on SARS-CoV-2 RBD with subnanomolar to low nanomolar affinities. Some of these antibodies neutralize SARS-CoV-2 by targeting a cryptic epitope located in the spike trimeric interface. Collectively, this work presents a versatile platform for rapid antibody isolation and identifies promising therapeutic anti-SARS-CoV-2 antibodies as well as the diverse immogneic profile of the spike protein.

Keywords: CR3022; RBD; SARS-CoV-2; nanobody; single-domain antibody; trimeric interface.

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology
  • Epitopes / immunology
  • Humans
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Models, Molecular
  • Peptide Library*
  • Protein Domains
  • Single-Domain Antibodies / chemistry
  • Single-Domain Antibodies / immunology
  • Single-Domain Antibodies / isolation & purification*
  • Spike Glycoprotein, Coronavirus / chemistry


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Peptide Library
  • Single-Domain Antibodies
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2