Frontiers in Immunology (Feb 2022)

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

  • Irina A. Favorskaya,
  • Dmitry V. Shcheblyakov,
  • Ilias B. Esmagambetov,
  • Inna V. Dolzhikova,
  • Irina A. Alekseeva,
  • Anastasia I. Korobkova,
  • Daria V. Voronina,
  • Ekaterina I. Ryabova,
  • Artem A. Derkaev,
  • Anna V. Kovyrshina,
  • Anna A. Iliukhina,
  • Andrey G. Botikov,
  • Olga L. Voronina,
  • Daria A. Egorova,
  • Olga V. Zubkova,
  • Natalia N. Ryzhova,
  • Ekaterina I. Aksenova,
  • Marina S. Kunda,
  • Denis Y. Logunov,
  • Boris S. Naroditsky,
  • Alexandr L. Gintsburg

DOI
https://doi.org/10.3389/fimmu.2022.822159
Journal volume & issue
Vol. 13

Abstract

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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.

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