An engineered bispecific nanobody in tetrameric secretory IgA format confers broad neutralization against SARS-CoV-1&2 and most variants DOI Creative Commons
Weihong Zeng, Xiaoying Jia, Xiangyang Chi

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 253, P. 126817 - 126817

Published: Sept. 9, 2023

SARS-CoV-2, a type of respiratory virus, has exerted great impact on global health and economy over the past three years. Antibody-based therapy was initially successful but later failed due to accumulation mutations in spike protein virus. Strategies that enable antibodies resist virus escape are therefore significance. Here, we engineer bispecific SARS-CoV-2 neutralizing nanobody secretory Immunoglobulin A (SIgA) format, named S2-3-IgA2m2, which shows broad potent neutralization against SARS-CoV-1, its variants concern (VOCs) including XBB BQ.1.1. S2-3-IgA2m2 is ∼1800-fold more than parental IgG counterpart XBB. stable mouse lungs at least for days when administrated by nasal delivery. In hamsters infected with BA.5, intranasal doses 1 mg/kg significantly reduce viral RNA loads completely eliminate infectious particles trachea lungs. Notably, even single dose mg/kg, prophylactically administered through route drastically reduces airway particles. This study provides an effective weapon combating proposes new strategy overcoming escape, lays strategic reserves rapid response potential future outbreaks "SARS-CoV-3".

Language: Английский

Small but Mighty: Nanobodies in the Fight Against Infectious Diseases DOI Creative Commons
Wenning Jiang, Chundong Huang, Serge Muyldermans

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 610 - 610

Published: April 23, 2025

Infectious diseases, caused by pathogenic microorganisms and capable of spreading, pose a significant threat to global public health. Developing efficient cost-effective techniques for treating infectious diseases is crucial in curbing their progression reducing patients’ morbidity mortality. Nanobodies (Nbs), novel class affinity reagents derived from unique heavy chain-only antibodies camelids, represent the smallest intact fully functional antigen-binding fragments. Compared with conventional antigen binding fragments, Nbs offer numerous advantages, including high affinity, exceptional target specificity, production, easy accessibility, robust stability, demonstrating immense potential disease treatment. This review introduces focuses on discussing mechanisms intervention strategies treatment viral bacterial infections.

Language: Английский

Citations

1
Therapeutic nanobodies against SARS-CoV-2 and other pathogenic human coronaviruses DOI Creative Commons
Yang Yang, Fang Li, Lanying Du

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 31, 2024

Abstract Nanobodies, single-domain antibodies derived from variable domain of camelid or shark heavy-chain antibodies, have unique properties with small size, strong binding affinity, easy construction in versatile formats, high neutralizing activity, protective efficacy, and manufactural capacity on a large-scale. Nanobodies been arisen as an effective research tool for development nanobiotechnologies variety applications. Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, MERS-CoV, caused serious outbreaks global pandemic, continue to post threat public health worldwide. The viral spike (S) protein its cognate receptor-binding (RBD), which initiate entry play critical role virus pathogenesis, are important therapeutic targets. This review describes human CoVs, including structures proteins, S protein-mediated process. It also summarizes recent advances nanobodies targeting these focusing those the RBD. Finally, we discuss potential strategies improve efficacy against emerging SARS-CoV-2 variants other CoVs pandemic potential. will provide information rational design evaluation agents reemerging pathogens. Graphical abstract

Language: Английский

Citations

9
Single domain antibody: Development and application in biotechnology and biopharma DOI Creative Commons

Ting Yu,

Fang Zheng, Wenbo He

et al.

Immunological Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Summary Heavy‐chain antibodies (HCAbs) are a unique type of devoid light chains, and comprised two heavy chains‐only that recognize their cognate antigen by virtue single variable domain also referred to as VHH, antibody (sdAb), or nanobody (Nb). These functional HCAbs, serendipitous discovered about three decades ago, exclusively found in camelids, comprising dromedaries, camels, llamas, vicugnas. Nanobodies have become an essential tool biomedical research medicine, both diagnostics therapeutics due beneficial properties: small size, high stability, strong antigen‐binding affinity, low immunogenicity, production cost, straightforward engineering into more potent affinity reagents. The occurrence HCAbs camelids remains intriguing. It is believed be evolutionary adaptation, equipping with robust adaptive immune defense suitable respond the pressure from pathogenic invasion necessitating profound recognition neutralization. This innovation led simplified HCAb structure, possibly supported genetic mutations drift, allowing mutation diversification chain gene constant regions. Beyond understanding origins, application nanobodies has significantly advanced over past 30 years. Alongside expanding laboratory research, there been rapid increase patent for nanobodies. introduction commercial drugs such Cablivi, Nanozora, Envafolimab, Carvykti boosted confidence among potential. review explores history ontogeny, applications biotechnology pharmaceuticals, focusing on approved ongoing medical pipelines.

Language: Английский

Citations

8
Adaptive multi-epitope targeting and avidity-enhanced nanobody platform for ultrapotent, durable antiviral therapy DOI
Yufei Xiang, Jialu Xu, Briana L. McGovern

et al.

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

7
Aptamers and Nanobodies as New Bioprobes for SARS-CoV-2 Diagnostic and Therapeutic System Applications DOI Creative Commons
Ki Sung Park, Tae-In Park,

Jae Eon Lee

et al.

Biosensors, Journal Year: 2024, Volume and Issue: 14(3), P. 146 - 146

Published: March 15, 2024

The global challenges posed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have underscored critical importance of innovative and efficient control systems for addressing future pandemics. most effective way to is rapidly suppress spread virus through early detection using a rapid, accurate, easy-to-use diagnostic platform. In biosensors that use bioprobes, binding affinity molecular recognition elements (MREs) primary factor determining dynamic range sensing Furthermore, sensitivity relies mainly on bioprobe quality with sufficient functionality. This comprehensive review investigates aptamers nanobodies recently developed as advanced MREs SARS-CoV-2 therapeutic applications. These bioprobes might be integrated into organic bioelectronic materials devices, promising enhanced specificity. offers valuable insights advancing biosensing technologies infectious disease diagnosis treatment new bioprobes.

Language: Английский

Citations

6
Fast and accurate modeling and design of antibody-antigen complex using tFold DOI Creative Commons
Fandi Wu, Yu Zhao, Jiaxiang Wu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 8, 2024

Abstract Accurate prediction of antibody-antigen complex structures holds significant potential for advancing biomedical research and the design therapeutic antibodies. Currently, structure protein monomers has achieved considerable success, promising progress been made in extending this achievement to complexes. However, despite these advancements, fast accurate remains a challenging unresolved issue. Existing end-to-end methods, which rely on homology templates, exhibit sub-optimal accuracy due absence co-evolutionary constraints. Meanwhile, conventional docking-based methods face difficulties identifying contact interface between antigen antibody require known individual components as inputs. In study, we present fully approach three-dimensional (3D) atomic-level predictions antibodies complexes, referred tFold-Ab tFold-Ag, respectively. tFold leverages large language model extract both intra-chain inter-chain residue-residue information, well evolutionary relationships, avoiding time-consuming multiple sequence alignment (MSA) search. Combined with specially designed modules such AI-driven flexible docking module, it achieves superior performance significantly enhanced speed predicting (1.6% RMSD reduction CDR-H3 region, thousand times faster) (37% increase DockQ score, over 10 faster), compared AlphaFold-Multimer. Given advantages, further extend capability structure-based virtual screening binding antibodies, de novo co-design The experiment results demonstrate high-throughput tool enhance processes involved tasks. To facilitate public access, release code offer web service antigen-antibody prediction, is available at https://drug.ai.tencent.com/en .

Language: Английский

Citations

5
Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain DOI Creative Commons
Bo Liu, Honghui Liu, Pu Han

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 13, 2024

Abstract Almost all the neutralizing antibodies targeting receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for development antibodies. Here, we present one nanobody, N235, displaying broad neutralization SARS-CoV-2 prototype multiple including newly Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in N-terminal (NTD) S protein, which interferes with RBD neighboring protein. The mechanism interpreted via flow cytometry Western blot shows appears to induce S1 subunit shedding from trimeric complex. Furthermore, nano-IgM construct (MN235), engineered by fusing human IgM Fc region, displays prevention inducing cross-linking virus particles. Compared MN235 exhibits varied enhancement pseudotyped authentic viruses vitro. intranasal administration low doses can effectively prevent infection sub-variant BA.1 XBB vivo, suggesting it be developed promising prophylactic antibody cope ongoing future infection.

Language: Английский

Citations

5
Serial Llama Immunization with Various SARS-CoV-2 RBD Variants Induces Broad Spectrum Virus-Neutralizing Nanobodies DOI Creative Commons

Pavel P. Solodkov,

Alexander M. Najakshin,

Nikolai A. Chikaev

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 129 - 129

Published: Jan. 26, 2024

The emergence of SARS-CoV-2 mutant variants has posed a significant challenge to both the prevention and treatment COVID-19 with anti-coronaviral neutralizing antibodies. latest viral demonstrate pronounced resistance vast majority human monoclonal antibodies raised against ancestral Wuhan variant. Less is known about susceptibility evolved virus camelid nanobodies developed at start pandemic. In this study, we compared nanobody repertoires in same llama after immunization Wuhan’s RBD variant subsequent serial variety variants, including that SARS-CoV-1. We show initial induced highly potent nanobodies, which efficiently protected Syrian hamsters from infection virus. These however, mostly lacked activity omicron-pseudotyped viruses. contrast, different resulted generation demonstrating higher degree somatic mutagenesis broad range neutralization. Four recognizing distinct epitopes were shown potently neutralize spectrum omicron those XBB sublineage. Our data broadly may be readily by immunization.

Language: Английский

Citations

4
Revolutionizing SARS-CoV-2 omicron variant detection: Towards faster and more reliable methods DOI
Dan Li, Cai Sun,

Pengfei Zhuang

et al.

Talanta, Journal Year: 2023, Volume and Issue: 266, P. 124937 - 124937

Published: July 12, 2023

Language: Английский

Citations

11
Therapeutic antibodies and alternative formats against SARS-CoV-2 DOI Creative Commons
Rahel R. Winiger, Laurent Perez

Antiviral Research, Journal Year: 2024, Volume and Issue: 223, P. 105820 - 105820

Published: Feb. 1, 2024

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) heavily burdened the entire world. Despite a prompt generation of vaccines and therapeutics to confront infection, virus remains threat. ancestor viral strain has evolved into several variants concern, with Omicron variant now having many distinct sublineages. Consequently, most available antibodies targeting spike went obsolete thus new therapies or therapeutic formats are needed. In this review we focus on antibody targets, provide an overview progress made so far, describe novel being explored, lessons learned from that can enhance preparedness.

Language: Английский

Citations

4