Single-Domain Antibodies Efficiently Neutralize SARS-CoV-2 Variants of Concern

Front Immunol. 2022 Feb 24;13:822159. doi: 10.3389/fimmu.2022.822159. eCollection 2022.


Virus-neutralizing antibodies are one of the few treatment options for COVID-19. The evolution of SARS-CoV-2 virus has led to the emergence of virus variants with reduced sensitivity to some antibody-based therapies. The development of potent antibodies with a broad spectrum of neutralizing activity is urgently needed. Here we isolated a panel of single-domain antibodies that specifically bind to the receptor-binding domain of SARS-CoV-2 S glycoprotein. Three of the selected antibodies exhibiting most robust neutralization potency were used to generate dimeric molecules. We observed that these modifications resulted in up to a 200-fold increase in neutralizing activity. The most potent heterodimeric molecule efficiently neutralized each of SARS-CoV-2 variant of concern, including Alpha, Beta, Gamma, Delta and Omicron variants. This heterodimeric molecule could be a promising drug candidate for a treatment for COVID-19 caused by virus variants of concern.

Keywords: COVID-19; SARS-CoV-2; VHH; VOC; nanobodies; neutralizing antibodies; single-domain antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / metabolism*
  • Antibodies, Viral / metabolism*
  • COVID-19 / immunology*
  • Epitopes / immunology
  • Humans
  • Neutralization Tests
  • SARS-CoV-2 / physiology*
  • Single-Domain Antibodies / genetics
  • Single-Domain Antibodies / metabolism*
  • Spike Glycoprotein, Coronavirus / immunology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Single-Domain Antibodies
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants