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A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding
The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identificati...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158119/ https://www.ncbi.nlm.nih.gov/pubmed/35663966 http://dx.doi.org/10.3389/fimmu.2022.820336 |
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author | Yang, Jing Lin, Sheng Sun, Honglu Chen, Zimin Yang, Fanli Lin, Xi Guo, Liyan Wang, Lingling Wen, Ao Zhang, Xindan Dai, Yushan He, Bin Cao, Yu Dong, Haohao Liu, Xianbo Chen, Bo Li, Jian Zhao, Qi Lu, Guangwen |
author_facet | Yang, Jing Lin, Sheng Sun, Honglu Chen, Zimin Yang, Fanli Lin, Xi Guo, Liyan Wang, Lingling Wen, Ao Zhang, Xindan Dai, Yushan He, Bin Cao, Yu Dong, Haohao Liu, Xianbo Chen, Bo Li, Jian Zhao, Qi Lu, Guangwen |
author_sort | Yang, Jing |
collection | PubMed |
description | The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identification and characterization of a potent SARS-CoV-2 neutralizing nanobody that targets the viral spike receptor-binding domain (S-RBD). The nanobody, termed as Nb-007, engages SARS-CoV-2 S-RBD with the two-digit picomolar binding affinity and shows outstanding virus entry-inhibition activity. The complex structure of Nb-007 bound to SARS-CoV-2 S-RBD reveals an epitope that is partially overlapping with the binding site for the human receptor of angiotensin-converting enzyme 2 (ACE2). The nanobody therefore exerts neutralization by competing with ACE2 for S-RBD binding, which is further ascertained by our in-vitro biochemical analyses. Finally, we also show that Nb-007 reserves promising, though compromised, neutralization activity against the currently-circulating Delta variant and that fusion of the nanobody with Fc dramatically increases its entry-inhibition capacity. Taken together, these data have paved the way of developing Nb-007 as a drug-reserve for potential treatment of SARS-CoV-2 related diseases. |
format | Online Article Text |
id | pubmed-9158119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91581192022-06-02 A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding Yang, Jing Lin, Sheng Sun, Honglu Chen, Zimin Yang, Fanli Lin, Xi Guo, Liyan Wang, Lingling Wen, Ao Zhang, Xindan Dai, Yushan He, Bin Cao, Yu Dong, Haohao Liu, Xianbo Chen, Bo Li, Jian Zhao, Qi Lu, Guangwen Front Immunol Immunology The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identification and characterization of a potent SARS-CoV-2 neutralizing nanobody that targets the viral spike receptor-binding domain (S-RBD). The nanobody, termed as Nb-007, engages SARS-CoV-2 S-RBD with the two-digit picomolar binding affinity and shows outstanding virus entry-inhibition activity. The complex structure of Nb-007 bound to SARS-CoV-2 S-RBD reveals an epitope that is partially overlapping with the binding site for the human receptor of angiotensin-converting enzyme 2 (ACE2). The nanobody therefore exerts neutralization by competing with ACE2 for S-RBD binding, which is further ascertained by our in-vitro biochemical analyses. Finally, we also show that Nb-007 reserves promising, though compromised, neutralization activity against the currently-circulating Delta variant and that fusion of the nanobody with Fc dramatically increases its entry-inhibition capacity. Taken together, these data have paved the way of developing Nb-007 as a drug-reserve for potential treatment of SARS-CoV-2 related diseases. Frontiers Media S.A. 2022-05-18 /pmc/articles/PMC9158119/ /pubmed/35663966 http://dx.doi.org/10.3389/fimmu.2022.820336 Text en Copyright © 2022 Yang, Lin, Sun, Chen, Yang, Lin, Guo, Wang, Wen, Zhang, Dai, He, Cao, Dong, Liu, Chen, Li, Zhao and Lu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Yang, Jing Lin, Sheng Sun, Honglu Chen, Zimin Yang, Fanli Lin, Xi Guo, Liyan Wang, Lingling Wen, Ao Zhang, Xindan Dai, Yushan He, Bin Cao, Yu Dong, Haohao Liu, Xianbo Chen, Bo Li, Jian Zhao, Qi Lu, Guangwen A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding |
title | A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding |
title_full | A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding |
title_fullStr | A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding |
title_full_unstemmed | A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding |
title_short | A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding |
title_sort | potent neutralizing nanobody targeting the spike receptor-binding domain of sars-cov-2 and the structural basis of its intimate binding |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158119/ https://www.ncbi.nlm.nih.gov/pubmed/35663966 http://dx.doi.org/10.3389/fimmu.2022.820336 |
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