The Broadly Neutralizing DEV_K57 Antibody, Isolated from a Convalescent Patient, in Complex with the SARS-CoV-2 RBD
- 1State Research Center of Virology and Biotechnology “Vector”, 630559 Kol’tsovo, Russia
- 2Moscow Center for Advanced Studies, 123592 Moscow, Russia
Abstract
The continuous evolution of SARS-CoV-2 necessitates broadly neutralizing antibodies for robust therapeutics. In this study, we isolated 1824 single B cells from a COVID-19 convalescent donor and obtained 91 pairs of nucleotide sequences potentially encoding VH/VL domains. From this library, we generated and evaluated a panel of 38 recombinant monoclonal antibodies. Among this panel, we identified DEV_K57 as a broadly neutralizing human IgG1 antibody targeting the SARS-CoV-2 RBD. DEV_K57 exhibited in vitro neutralization breadth against diverse variants, demonstrating subnanomolar IC50 values. This in vitro efficacy was translated in vivo. In a Syrian hamster model of SARS-CoV-2 Delta infection, DEV_K57 significantly reduced viral RNA and infectious titers in both the upper and lower respiratory tracts, conferring a favorable safety profile with minimal histopathological damage. To elucidate its mechanism, we performed comprehensive biophysical and structural analyses. Biolayer interferometry revealed a high picomolar binding affinity to the RBD Delta. Furthermore, size-exclusion chromatography coupled with small-angle X-ray scattering and computational modeling uncovered a unique, stable dimeric architecture of the DEV_K57 Fab-RBD complex in solution, with a binding interface distinct from previously characterized structures. These findings underscore the value of rapid antibody isolation for pandemic preparedness against future emerging biological threats.
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BibTeX
@article{sinitsina2026broadly,
title = {{The Broadly Neutralizing DEV_K57 Antibody, Isolated from a Convalescent Patient, in Complex with the SARS-CoV-2 RBD}},
author = {Elina V. Sinitsina and Ilnaz R. Imatdinov and Vitaliy Y. Tuyrin and Andrey V. Shipovalov and Anna V. Zaykovskaya and Irina A. Osinkina and Alexey O. Yanshin and Nikita S. Radchenko and Yury L. Ryzhykau and Vsevolod V. Sudarev and Daria D. Kuklina and Galina S. Onkhonova and Elena K. Ivleva and Alexander P. Agafonov and Anastasia V. Gladysheva},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219445},
url = {https://www.mdpi.com/1422-0067/27/21/9445},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Broadly Neutralizing DEV_K57 Antibody, Isolated from a Convalescent Patient, in Complex with the SARS-CoV-2 RBD
AU - Elina V. Sinitsina
AU - Ilnaz R. Imatdinov
AU - Vitaliy Y. Tuyrin
AU - Andrey V. Shipovalov
AU - Anna V. Zaykovskaya
AU - Irina A. Osinkina
AU - Alexey O. Yanshin
AU - Nikita S. Radchenko
AU - Yury L. Ryzhykau
AU - Vsevolod V. Sudarev
AU - Daria D. Kuklina
AU - Galina S. Onkhonova
AU - Elena K. Ivleva
AU - Alexander P. Agafonov
AU - Anastasia V. Gladysheva
PY - 2026
DA - 2026/10/23
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219445
UR - https://www.mdpi.com/1422-0067/27/21/9445
AB - The continuous evolution of SARS-CoV-2 necessitates broadly neutralizing antibodies for robust therapeutics. In this study, we isolated 1824 single B cells from a COVID-19 convalescent donor and obtained 91 pairs of nucleotide sequences potentially encoding VH/VL domains. From this library, we generated and evaluated a panel of 38 recombinant monoclonal antibodies. Among this panel, we identified DEV_K57 as a broadly neutralizing human IgG1 antibody targeting the SARS-CoV-2 RBD. DEV_K57 exhibited in vitro neutralization breadth against diverse variants, demonstrating subnanomolar IC50 values. This in vitro efficacy was translated in vivo. In a Syrian hamster model of SARS-CoV-2 Delta infection, DEV_K57 significantly reduced viral RNA and infectious titers in both the upper and lower respiratory tracts, conferring a favorable safety profile with minimal histopathological damage. To elucidate its mechanism, we performed comprehensive biophysical and structural analyses. Biolayer interferometry revealed a high picomolar binding affinity to the RBD Delta. Furthermore, size-exclusion chromatography coupled with small-angle X-ray scattering and computational modeling uncovered a unique, stable dimeric architecture of the DEV_K57 Fab-RBD complex in solution, with a binding interface distinct from previously characterized structures. These findings underscore the value of rapid antibody isolation for pandemic preparedness against future emerging biological threats.
SN - 1422-0067
ER -