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A bivalent spike-targeting nanobody with anti-sarbecovirus activity.

作者信息

Swart Iris C, Debski-Antoniak Oliver J, Zegar Aneta, de Bouter Thijs, Chatziandreou Marianthi, van den Berg Max, Drulyte Ieva, Pyrć Krzysztof, de Haan Cornelis A M, Hurdiss Daniel L, Bosch Berend-Jan, Oliveira Sabrina

机构信息

Cell Biology, Neurobiology and Biophysics, Department of Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands.

Virology Section, Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

出版信息

J Nanobiotechnology. 2025 Mar 10;23(1):196. doi: 10.1186/s12951-025-03243-y.


DOI:10.1186/s12951-025-03243-y
PMID:40059135
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11892322/
Abstract

The continued emergence and zoonotic threat posed by coronaviruses highlight the urgent need for effective antiviral strategies with broad reactivity to counter new emerging strains. Nanobodies (or single-domain antibodies) are promising alternatives to traditional monoclonal antibodies, due to their small size, cost-effectiveness and ease of bioengineering. Here, we describe 7F, a llama-derived nanobody, targeting the spike receptor binding domain of sarbecoviruses and SARS-like coronaviruses. 7F demonstrates potent neutralization against SARS-CoV-2 and cross-neutralizing activity against SARS-CoV and SARS-like CoV WIV16 pseudoviruses. Structural analysis reveals 7F's ability to induce the formation of spike trimer dimers by engaging with two SARS-CoV-2 spike RBDs, targeting the highly conserved class IV region, though concentration dependent. Bivalent 7F constructs substantially enhance neutralization potency and breadth, up to more recent SARS-CoV-2 variants of concern. Furthermore, we demonstrate the therapeutic potential of bivalent 7F against SARS-CoV-2 in the fully differentiated 3D tissue cultures mirroring the epithelium of the human airway ex vivo. The broad sarbecovirus activity and distinctive structural features of bivalent 7F underscore its potential as promising antiviral against emerging and evolving sarbecoviruses.

摘要

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本文引用的文献

[1]
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Front Mol Biosci. 2024-5-9

[2]
Discovery and multimerization of cross-reactive single-domain antibodies against SARS-like viruses to enhance potency and address emerging SARS-CoV-2 variants.

Sci Rep. 2023-8-22

[3]
Broad Sarbecovirus Neutralizing Antibodies Obtained by Computational Design and Synthetic Library Screening.

J Virol. 2023-7-27

[4]
Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity.

Nat Commun. 2023-2-3

[5]
Two pan-SARS-CoV-2 nanobodies and their multivalent derivatives effectively prevent Omicron infections in mice.

Cell Rep Med. 2023-2-21

[6]
Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses.

Nat Commun. 2022-12-27

[7]
A bispecific nanobody dimer broadly neutralizes SARS-CoV-1 & 2 variants of concern and offers substantial protection against Omicron via low-dose intranasal administration.

Cell Discov. 2022-12-9

[8]
The interplay between the airway epithelium and tissue macrophages during the SARS-CoV-2 infection.

Front Immunol. 2022

[9]
Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses.

Nat Rev Immunol. 2023-3

[10]
Evolution of Anti-SARS-CoV-2 Therapeutic Antibodies.

Int J Mol Sci. 2022-8-28

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