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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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