Broadly neutralizing single-domain antibody targeting the spike NTD displays therapeutic efficacy against diverse SARS-CoV-2 variants
The continuous evolution of SARS-CoV-2 virus has led to the emergence of multiple Omicron descendants resistant to previously approved therapeutic antibodies. Therefore, cross-reactive antibodies to conserved neutralizing epitopes are urgently needed to protect immunocompromised patients and individuals at high risk of severe COVID-19. Here we report the characterization of 1p2B5, a single-domain antibody targeting N-terminal domain (NTD) of SARS-CoV-2 S protein. 1p2B5 exerts broad neutralizing activity against diverse SARS-CoV-2 variants. The Fc-fused form of the antibody demonstrates enhanced neutralizing potency in vitro , inhibiting both the earliest and currently circulating subvariants with nanomolar activity. Systemic therapeutic administration of 1p2B5-Fc at a dose of 1 mg/kg protects Syrian hamsters and hACE2-transgenic mice from challenge with evolutionarily distant SARS-CoV-2 variants. Our findings highlight the potential of NTD-specific monoclonal antibodies for prophylaxis and therapeutic intervention.
Authors
- Vilen Azizyan (ORCID: https://orcid.org/0000-0001-9718-6099)
- Artem A. Derkaev (ORCID: https://orcid.org/0000-0003-3776-3856)
- Anastasia I. Korobkova (ORCID: https://orcid.org/0000-0001-9489-4305)
- E. I. Ryabova (ORCID: https://orcid.org/0000-0002-2687-5185)
- Daria V. Voronina (ORCID: https://orcid.org/0000-0001-6629-744X)
- I. B. Esmagambetov (ORCID: https://orcid.org/0000-0002-2063-2449)
- I. A. FAVORSKAYA (ORCID: https://orcid.org/0000-0003-0639-8390)
- V. V. Prokofiev (ORCID: https://orcid.org/0000-0002-4130-177X)
- Amir I. Tukhvatulin (ORCID: https://orcid.org/0000-0001-8506-2339)
- Daria M. Grousova (ORCID: https://orcid.org/0000-0002-3299-4818)
- Ilya D. Zorkov (ORCID: https://orcid.org/0000-0001-8311-2283)
- Anna A. Iliukhina (ORCID: https://orcid.org/0000-0003-0728-5478)
- Alina S. Dzharullaeva (ORCID: https://orcid.org/0000-0003-1743-0798)
- Olga V. Zubkova (ORCID: https://orcid.org/0000-0001-7893-8419)
- D. Y. Logunov
- Irina A. Alekseeva
- Inna V. Shuliakova
- Dmitry V. Shcheblyakov
Institutions
- Ministry of Health of the Russian Federation (RU)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2026-03-23
- DOI
- https://doi.org/10.3389/fimmu.2026.1799333
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00