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.
Copyright © 2022 Favorskaya, Shcheblyakov, Esmagambetov, Dolzhikova, Alekseeva, Korobkova, Voronina, Ryabova, Derkaev, Kovyrshina, Iliukhina, Botikov, Voronina, Egorova, Zubkova, Ryzhova, Aksenova, Kunda, Logunov, Naroditsky and Gintsburg.