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Single-domain antibodies efficiently neutralize SARS-CoV-2 variants of concern, including Omicron variant

Favorskaya, I. A.; Shcheblyakov, D. V.; Esmagambetov, I. B.; Dolzhikova, I. V.; Alekseeva, I. A.; Korobkova, A. I.; Voronina, D. V.; Ryabova, E. I.; Derkaev, A. A.; Kovyrshina, A. V.; Iliukhina, A. A.; Botikov, A. G.; Voronina, O. L.; Egorova, D. A.; Zubkova, O. V.; Ryzhova, N. N.; Aksenova, E. I.; Kunda, M. S.; Logunov, D. Y.; Naroditsky, B. S.; Gintsburg, A. L.

2021-12-23 immunology
10.1101/2021.11.24.469842 bioRxiv
Show 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.

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