Open Access

PLoS Pathogens, volume 17, issue 3, pages e1009328

A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2

Hebang Yao ¹

Hongmin Cai ¹

Tingting Li ¹

Bingjie Zhou ²

Wenming Qin ³

Dimitri Lavillette ²

Dianfan Li ¹

Hide authors affiliations Show authors affiliations: 3 affiliations

CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China, |

University of Chinese Academy of Sciences, Beijing, China, |

National Facility for Protein Science in Shanghai, Shanghai Advanced Research Institute (Zhangjiang Laboratory), Chinese Academy of Sciences, Shanghai, China |

Publication type: Journal Article

Publication date: 2021-03-03

Public Library of Science (PLoS)

Journal: PLoS Pathogens

Quartile SCImago

Quartile WOS

Impact factor: 6.7

ISSN: 15537366, 15537374

DOI: 10.1371/journal.ppat.1009328

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Molecular Biology

Genetics

Microbiology

Immunology

Parasitology

Virology

Abstract

A key step to the SARS-CoV-2 infection is the attachment of its Spike receptor-binding domain (S RBD) to the host receptor ACE2. Considerable research has been devoted to the development of neutralizing antibodies, including llama-derived single-chain nanobodies, to target the receptor-binding motif (RBM) and to block ACE2-RBD binding. Simple and effective strategies to increase potency are desirable for such studies when antibodies are only modestly effective. Here, we identify and characterize a high-affinity synthetic nanobody (sybody, SR31) as a fusion partner to improve the potency of RBM-antibodies. Crystallographic studies reveal that SR31 binds to RBD at a conserved and ‘greasy’ site distal to RBM. Although SR31 distorts RBD at the interface, it does not perturb the RBM conformation, hence displaying no neutralizing activities itself. However, fusing SR31 to two modestly neutralizing sybodies dramatically increases their affinity for RBD and neutralization activity against SARS-CoV-2 pseudovirus. Our work presents a tool protein and an efficient strategy to improve nanobody potency.

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Citations by journals

	1 2
Nature Communications	Nature Communications, 2, 5.13% Nature Communications 2 publications, 5.13%
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Communications Biology	Communications Biology, 2, 5.13% Communications Biology 2 publications, 5.13%
Advanced Biotechnology	Advanced Biotechnology, 2, 5.13% Advanced Biotechnology 2 publications, 5.13%
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 1, 2.56% International Journal of Molecular Sciences 1 publication, 2.56%
Frontiers in Microbiology	Frontiers in Microbiology, 1, 2.56% Frontiers in Microbiology 1 publication, 2.56%
Frontiers in Immunology	Frontiers in Immunology, 1, 2.56% Frontiers in Immunology 1 publication, 2.56%
Frontiers in Drug Discovery	Frontiers in Drug Discovery, 1, 2.56% Frontiers in Drug Discovery 1 publication, 2.56%
Microbial Cell Factories	Microbial Cell Factories, 1, 2.56% Microbial Cell Factories 1 publication, 2.56%
Molecular Biology Reports	Molecular Biology Reports, 1, 2.56% Molecular Biology Reports 1 publication, 2.56%
Cell Research	Cell Research, 1, 2.56% Cell Research 1 publication, 2.56%
Signal Transduction and Targeted Therapy	Signal Transduction and Targeted Therapy, 1, 2.56% Signal Transduction and Targeted Therapy 1 publication, 2.56%
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International Journal of Surgery	International Journal of Surgery, 1, 2.56% International Journal of Surgery 1 publication, 2.56%
Analytical Biochemistry	Analytical Biochemistry, 1, 2.56% Analytical Biochemistry 1 publication, 2.56%
International Journal of Biological Macromolecules	International Journal of Biological Macromolecules, 1, 2.56% International Journal of Biological Macromolecules 1 publication, 2.56%
Small	Small, 1, 2.56% Small 1 publication, 2.56%
iScience	iScience, 1, 2.56% iScience 1 publication, 2.56%
Molecular Diagnosis and Therapy	Molecular Diagnosis and Therapy, 1, 2.56% Molecular Diagnosis and Therapy 1 publication, 2.56%
Fish and Shellfish Immunology	Fish and Shellfish Immunology, 1, 2.56% Fish and Shellfish Immunology 1 publication, 2.56%
Journal of Chemical Information and Modeling	Journal of Chemical Information and Modeling, 1, 2.56% Journal of Chemical Information and Modeling 1 publication, 2.56%
ACS Infectious Diseases	ACS Infectious Diseases, 1, 2.56% ACS Infectious Diseases 1 publication, 2.56%
ACS Applied Bio Materials	ACS Applied Bio Materials, 1, 2.56% ACS Applied Bio Materials 1 publication, 2.56%
mAbs	mAbs, 1, 2.56% mAbs 1 publication, 2.56%
EMBO Reports	EMBO Reports, 1, 2.56% EMBO Reports 1 publication, 2.56%
EMBO Molecular Medicine	EMBO Molecular Medicine, 1, 2.56% EMBO Molecular Medicine 1 publication, 2.56%
ACS applied materials & interfaces	ACS applied materials & interfaces, 1, 2.56% ACS applied materials & interfaces 1 publication, 2.56%
Current Clinical Microbiology Reports	Current Clinical Microbiology Reports, 1, 2.56% Current Clinical Microbiology Reports 1 publication, 2.56%
Russian Chemical Reviews	Russian Chemical Reviews, 1, 2.56% Russian Chemical Reviews 1 publication, 2.56%
	1 2

Citations by publishers

	2 4 6 8 10 12
Springer Nature	Springer Nature, 12, 30.77% Springer Nature 12 publications, 30.77%
Elsevier	Elsevier, 6, 15.38% Elsevier 6 publications, 15.38%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 6, 15.38% Cold Spring Harbor Laboratory 6 publications, 15.38%
American Chemical Society (ACS)	American Chemical Society (ACS), 4, 10.26% American Chemical Society (ACS) 4 publications, 10.26%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 3, 7.69% Multidisciplinary Digital Publishing Institute (MDPI) 3 publications, 7.69%
Frontiers Media S.A.	Frontiers Media S.A., 3, 7.69% Frontiers Media S.A. 3 publications, 7.69%
EMBO press	EMBO press, 2, 5.13% EMBO press 2 publications, 5.13%
Wiley	Wiley, 1, 2.56% Wiley 1 publication, 2.56%
Taylor & Francis	Taylor & Francis, 1, 2.56% Taylor & Francis 1 publication, 2.56%
Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii	Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii, 1, 2.56% Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii 1 publication, 2.56%
	2 4 6 8 10 12

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Yao H. et al. A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2 // PLoS Pathogens. 2021. Vol. 17. No. 3. p. e1009328.

GOST all authors (up to 50) Copy

Yao H., Cai H., Li T., Zhou B., Qin W., Lavillette D., Li D. A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2 // PLoS Pathogens. 2021. Vol. 17. No. 3. p. e1009328.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1371/journal.ppat.1009328

UR - https://doi.org/10.1371/journal.ppat.1009328

TI - A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2

T2 - PLoS Pathogens

AU - Yao, Hebang

AU - Cai, Hongmin

AU - Li, Tingting

AU - Zhou, Bingjie

AU - Qin, Wenming

AU - Lavillette, Dimitri

AU - Li, Dianfan

PY - 2021

DA - 2021/03/03 00:00:00

PB - Public Library of Science (PLoS)

SP - e1009328

IS - 3

VL - 17

SN - 1553-7366

SN - 1553-7374

ER -

BibTex |

Cite this

BibTex Copy

@article{2021_Yao,

author = {Hebang Yao and Hongmin Cai and Tingting Li and Bingjie Zhou and Wenming Qin and Dimitri Lavillette and Dianfan Li},

title = {A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2},

journal = {PLoS Pathogens},

year = {2021},

volume = {17},

publisher = {Public Library of Science (PLoS)},

month = {mar},

url = {https://doi.org/10.1371/journal.ppat.1009328},

number = {3},

pages = {e1009328},

doi = {10.1371/journal.ppat.1009328}

}

MLA

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MLA Copy

Yao, Hebang, et al. “A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2.” PLoS Pathogens, vol. 17, no. 3, Mar. 2021, p. e1009328. https://doi.org/10.1371/journal.ppat.1009328.

Found error?

Publisher

Public Library of Science (PLoS)

Journal

PLoS Pathogens

Quartile SCImago

Quartile WOS

Impact factor

6.7

ISSN

15537366 (Print)
15537374 (Electronic)

Profiles

Lavillette, Dimitri