Single-Domain Antibodies Efficiently Neutralize SARS-CoV-2 Variants of Concern
I. A. FAVORSKAYA, Dmitry V. Shcheblyakov, I. B. Esmagambetov, Inna V. Dolzhikova, Irina A Alekseeva, Anastasia I. Korobkova, Daria V. Voronina, E. I. Ryabova, Artem A. Derkaev, Anna V. Kovyrshina, Anna A. Iliukhina, Andrey G. Botikov, Olga L. Voronina, Daria A. Egorova, Olga V. Zubkova, Н. Н. Рыжова, Ekaterina I. Aksenova, Marina S. Kunda, Denis Y. Logunov, Boris S. Naroditsky, A. Gintsburg
Abstract
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.