Aptamers and Nanobodies as New Bioprobes for SARS-CoV-2 Diagnostic and Therapeutic System Applications

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

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Nanobody engineering: computational modelling and design for biomedical and therapeutic applications

FEBS Open Bio, Journal Year: 2024, Volume and Issue: 15(2), P. 236 - 253

Published: June 19, 2024

Nanobodies, the smallest functional antibody fragment derived from camelid heavy-chain-only antibodies, have emerged as powerful tools for diverse biomedical applications. In this comprehensive review, we discuss structural characteristics, properties, and computational approaches driving design optimisation of synthetic nanobodies. We explore their unique antigen-binding domains, highlighting critical role complementarity-determining regions in target recognition specificity. This review further underscores advantages nanobodies over conventional antibodies a biosynthesis perspective, including small size, stability, solubility, which make them ideal candidates economical antigen capture diagnostics, therapeutics, biosensing. recent advancements methods nanobody modelling, epitope prediction, affinity maturation, shedding light on intricate mechanisms conformational dynamics. Finally, examine direct example how strategies were implemented improving nanobody-based immunosensor, known Quenchbody. Through combining experimental findings insights, elucidates transformative impact biotechnology research, offering roadmap future applications healthcare diagnostics.

Language: Английский

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SARS-CoV-2 Specific Nanobodies Neutralize Different Variants of Concern and Reduce Virus Load in the Brain of h-ACE2 Transgenic Mice

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 185 - 185

Published: Jan. 25, 2024

Since the beginning of COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines combat disease. In this work, we developed llama-derived nanobodies (Nbs) directed against receptor binding domain (RBD) other domains Spike (S) protein SARS-CoV-2. Most Nbs with neutralizing properties were RBD able block S-2P/ACE2 interaction. Three recognized N-terminal (NTD) S-2P protein. Intranasal administration induced protection ranging from 40% 80% after challenge WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, was associated reduction virus replication nasal turbinates load brain. Employing pseudovirus neutralization assays, identified capacity Alpha, Beta, Delta, Omicron variants, including Nb capable all variants tested. Furthermore, cocktails different performed better than individual at two (B.1.529 BA.2). Altogether, data suggest potential SARS-CoV-2 specific for intranasal treatment encephalitis.

Language: Английский

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Recombinant Antibody Fragments for Immunotherapy of Parkinson’s Disease

BioDrugs, Journal Year: 2024, Volume and Issue: 38(2), P. 249 - 257

Published: Jan. 27, 2024

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. Multiple genetic and environmental factors leading to progressive loss of dopaminergic neurons in substantia nigra pars compacta (SN) consequent depletion dopamine were described. Current clinical approaches, such as replacement or deep brain stimulation using surgically implanted probes, provide symptomatic relief but cannot modify progression. Therefore, disease-modifying therapeutic tools are urgently needed. Immunotherapy including passive transfer protective antibodies their fragments, have shown efficacy several animal models diseases, PD. Recombinant antibody fragments promising alternatives conventional full-length antibodies. Modern computational approaches molecular biology tools, directed evolution methodology, design tissue-penetrating fusion peptides allowed for development recombinant with superior specificity affinity, reduced immunogenicity, capacity target hidden epitopes cross blood-brain barrier (BBB), higher solubility stability, ability refold after heat denaturation, inexpensive large-scale production. In addition, do not induce microglia Fcγ receptor (FcγR)-mediated proinflammatory response tissue damage central nervous system (CNS), because they lack Fc portion immunoglobulin molecule. present review, we summarized data on evaluated immunotherapeutics preclinical PD discussed potential developing preventive protocols patients

Language: Английский

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Nanobody in a Double “Y”-Shaped Assembly: A Promising Candidate for Lateral Flow Immunoassays

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(18), P. 7130 - 7137

Published: April 29, 2024

Derived from camelid heavy-chain antibodies, nanobodies (Nbs) are the smallest natural antibodies and an ideal tool in biological studies because of their simple structure, high yield, low cost. Nbs possess significant potential for developing highly specific user-friendly diagnostic assays. Despite offering considerable advantages detection applications, knowledge is limited regarding exclusive use lateral flow immunoassay (LFIA) detection. Herein, we present a novel double "Y" architecture, achieved by using SpyTag/SpyCatcher Im7/CL7 systems. The assemblies exhibited significantly higher affinity epitopes, as particularly evident reduced dissociation rate. An LFIA employing was effectively used to detect severe acute respiratory syndrome coronavirus-2 N protein, with limit at least 500 pg/mL. This study helps broaden array tools available development Nb-based techniques.

Language: Английский

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Nanoscale warriors against viral invaders: a comprehensive review of Nanobodies as potential antiviral therapeutics

mAbs, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 9, 2025

Viral infections remain a significant global health threat, with emerging and reemerging viruses causing epidemics pandemics. Despite advancements in antiviral therapies, the development of effective treatments is often hindered by challenges, such as viral resistance emergence new strains. In this context, novel therapeutic modalities essential to combat notorious viruses. While traditional monoclonal antibodies are widely used for treatment several diseases, nanobodies derived from heavy chain-only have emerged promising "nanoscale warriors" against infections. Nanobodies possess unique structural properties that enhance their ability recognize diverse epitopes. Their small size also imparts properties, improved bioavailability, solubility, stability, proteolytic resistance, making them an ideal class therapeutics review, we discuss role antivirals various Techniques developing nanobodies, delivery strategies covered, challenges opportunities associated use therapies discussed. We offer insights into future nanobody-based research support managing

Language: Английский

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Revolutionizing antiviral therapy with nanobodies: Generation and prospects

Biotechnology Reports, Journal Year: 2023, Volume and Issue: 39, P. e00803 - e00803

Published: June 8, 2023

As the world continues to grapple with infectious diseases, scientists are constantly searching for effective ways combat these deadly pathogens. One promising avenue of research is use nanobodies as neutralization agents. These small proteins, derived from camelid antibodies, have several unique advantages over traditional including their size. Nanobodies much smaller than conventional typically weighing in at around 15 kDa compared 150 a typical human antibody. This size allows them penetrate into tight spaces that larger molecules cannot reach, such crevices on surface viruses or bacteria. makes highly neutralizing by binding and blocking key functional sites. In this mini-review we discuss construction approaches nanobodies, some methods increase half-life nanobodies. Moreover, therapeutic potential

Language: Английский

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Targets for the diagnosis of Acanthamoeba eye infections include four cyst wall proteins and the mannose-binding domain of the trophozoite mannose-binding protein

mSphere, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

ABSTRACT Acanthamoebae , which are free-living amoebae, cause corneal inflammation (keratitis) and blindness, if not quickly diagnosed effectively treated. The walls of Acanthamoeba cysts contain cellulose have two layers connected by conical ostioles. Cysts identified in vivo confocal microscopy the eye or calcofluor-white- Giemsa-labeling scrapings, both demand great expertise. Trophozoites, use a mannose-binding protein to adhere keratinocytes, cultures that delay diagnosis treatment. We recently used structural experimental methods characterize cellulose-binding domains Luke Leo lectins, abundant inner layer However, no antibodies been made these lectins Jonah lectin laccase, outer layer. Here, rabbit (rAbs) recombinant Luke, Leo, Jonah, laccase supported localizations GFP-tagged proteins transfected . rAbs efficiently detected calcofluor white-labeled 10 11 isolates tested, including six T4 genotypes most cases keratitis. Further, shed into medium during encystation was an enzyme-linked immunoassay. Structural domain (ManBD) protein, while ManBD DAPI-labeled trophozoites from all tested. conclude four cyst wall identify trophozoites, respectively. IMPORTANCE Free-living amoeba soil water keratitis, is identification unlabeled calcofluor-white (CFW) labeled fluorescence scrapings. Alternatively, infections cultures. we showed (Jonah, laccase) each CFW-labeled released encysting also mediates adherence In summary, appear be excellent targets for

Language: Английский

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Interaction of SARS-CoV-2 with host cells and antibodies: experiment and simulation

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(18), P. 6497 - 6553

Published: Jan. 1, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of devastating global COVID-19 pandemic announced by WHO in March 2020.

Language: Английский

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Mono- and Bi-specific Nanobodies Targeting the CUB Domains of PCPE-1 Reduce the Proteolytic Processing of Fibrillar Procollagens

Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(16), P. 168667 - 168667

Published: June 18, 2024

The excessive deposition of fibrillar collagens is a hallmark fibrosis. Collagen fibril formation requires proteolytic maturations by Procollagen N- and C-proteinases (PNPs PCPs) to remove the C-propeptides which maintain procollagens in soluble form. C-Proteinase Enhancer–1 (PCPE-1, glycoprotein composed two CUB one NTR domains) regulatory protein that activates C-terminal processing main PCPs. It often up-regulated fibrotic diseases represents promising target for development novel anti-fibrotic strategies. Here, our objective was develop first antagonists PCPE-1, based on nanobody scaffold. Using both an vivo selection through immunization llama vitro with synthetic library, we generated 18 nanobodies directed against domains PCPE1, carry its enhancing activity. Among them, I5 from immune library H4 have high affinity PCPE-1 inhibit interaction procollagens. crystal structure complex formed showed they distinct epitopes enabled design biparatopic fusion, diabody diab-D1. Diab-D1 has sub-nanomolar potent antagonist activity, preventing stimulation procollagen cleavage vitro. Moreover, also effective reducing maturation I cultures human dermal fibroblasts hence holds great promise as tool modulate collagen conditions.

Language: Английский

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