tetano
Editor, Senior Moderator
Front Immunol
. 2026 Mar 23:17:1799333.
doi: 10.3389/fimmu.2026.1799333. eCollection 2026.
Broadly neutralizing single-domain antibody targeting the spike NTD displays therapeutic efficacy against diverse SARS-CoV-2 variants
Anastasia I Korobkova[SUP] 1 [/SUP], Irina A Favorskaya[SUP] 2 [/SUP], Inna V Shuliakova[SUP] 3 [/SUP], Anna A Iliukhina[SUP] 3 [/SUP], Daria M Grousova[SUP] 3 [/SUP], Irina A Alekseeva[SUP] 1 [/SUP], Ekaterina I Ryabova[SUP] 1 [/SUP], Artem A Derkaev[SUP] 1 [/SUP], Valentin V Azizyan[SUP] 3 [/SUP], Ilya D Zorkov[SUP] 3 [/SUP], Alina S Dzharullaeva[SUP] 4 [/SUP], Amir I Tukhvatulin[SUP] 4 [/SUP], Ilias B Esmagambetov[SUP] 5 [/SUP], Vladimir V Prokofiev[SUP] 1 [/SUP], Daria V Voronina[SUP] 1 [/SUP], Olga V Zubkova[SUP] 1 [/SUP], Dmitry V Shcheblyakov[SUP] 1 [/SUP], Denis Y Logunov[SUP] 4 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; broadly neutralizing antibodies; sdAbs; single-domain antibodies; therapeutic efficacy.
. 2026 Mar 23:17:1799333.
doi: 10.3389/fimmu.2026.1799333. eCollection 2026.
Broadly neutralizing single-domain antibody targeting the spike NTD displays therapeutic efficacy against diverse SARS-CoV-2 variants
Anastasia I Korobkova[SUP] 1 [/SUP], Irina A Favorskaya[SUP] 2 [/SUP], Inna V Shuliakova[SUP] 3 [/SUP], Anna A Iliukhina[SUP] 3 [/SUP], Daria M Grousova[SUP] 3 [/SUP], Irina A Alekseeva[SUP] 1 [/SUP], Ekaterina I Ryabova[SUP] 1 [/SUP], Artem A Derkaev[SUP] 1 [/SUP], Valentin V Azizyan[SUP] 3 [/SUP], Ilya D Zorkov[SUP] 3 [/SUP], Alina S Dzharullaeva[SUP] 4 [/SUP], Amir I Tukhvatulin[SUP] 4 [/SUP], Ilias B Esmagambetov[SUP] 5 [/SUP], Vladimir V Prokofiev[SUP] 1 [/SUP], Daria V Voronina[SUP] 1 [/SUP], Olga V Zubkova[SUP] 1 [/SUP], Dmitry V Shcheblyakov[SUP] 1 [/SUP], Denis Y Logunov[SUP] 4 [/SUP]
Affiliations
- PMID: 41948332
- PMCID: PMC13050822
- DOI: 10.3389/fimmu.2026.1799333
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.
Keywords: COVID-19; SARS-CoV-2; broadly neutralizing antibodies; sdAbs; single-domain antibodies; therapeutic efficacy.