Nanobodies: COVID-19 and Future Perspectives

Nieto, Guillermo Valenzuela; Miranda-Chacón, Zaray; Salinas-Rebolledo, Constanza; Jara, Ronald; Cuevas, Alexei; Berking, Anne; Rojas-Fernández, Alejandro

doi:10.3389/fddsv.2022.927164

Cited by 13 publications

(7 citation statements)

References 169 publications

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“…This was achieved through biopanning of existing libraries for MERS and SARS coronavirus or immunizing llamas and alpacas with multiple SARS-CoV-2 antigens, primarily S and RBD recombinant proteins [28][29][30][31][32][33][34][35][36][37] . So far, several Nbs have been developed with promising diagnostic and therapeutic applications [20,38]. Both monomeric Nbs and engineered molecules showed strong neutralizing activity to the different VOCs that have emerged, including the Omicron variants [39][40][41][42][43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Nanobodies against SARS-CoV-2 reduced virus load in the brain of challenged mice and neutralized Wuhan, Delta and Omicron Variants

Pavan

Bok

Juan

et al. 2023

Preprint

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In this work, we developed llama-derived nanobodies (Nbs) directed to the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Nanobodies were selected after the biopanning of two Nb-libraries, one of which was generated after the immunization of a llama (lama glama) with the bovine coronavirus (BCoV) Mebus, and another with the full-length pre-fused locked S protein (S-2P) and the RBD from the SARS-CoV-2 Wuhan strain (WT). Most of the neutralizing Nbs selected with either RBD or S-2P from SARS-CoV-2 were directed to RBD and were able to block S2P/ACE2 interaction. Three Nbs recognized the N-terminal domain (NTD) of the S-2P protein as measured by competition with biliverdin, while some non-neutralizing Nbs recognize epitopes in the S2 domain. One Nb from the BCoV immune library was directed to RBD but was non-neutralizing. Intranasal administration of Nbs induced protection ranging from 40% to 80% against COVID-19 death in k18-hACE2 mice challenged with the WT strain. Interestingly, protection was not only associated with a significant reduction of virus replication in nasal turbinates and lungs, but also with a reduction of virus load in the brain. Employing pseudovirus neutralization assays, we were able to identify Nbs with neutralizing capacity against the Alpha, Beta, Delta and Omicron variants. Furthermore, cocktails of different Nbs performed better than individual Nbs to neutralize two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest these Nbs can potentially be used as a cocktail for intranasal treatment to prevent or treat COVID-19 encephalitis, or modified for prophylactic administration to fight this disease.

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Section: Discussionmentioning

confidence: 99%

Nanobodies against SARS-CoV-2 reduced virus load in the brain of challenged mice and neutralized Wuhan, Delta and Omicron Variants

Pavan

Bok

Juan

et al. 2023

Preprint

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“…515 Additional advantages of Nbs over Abs are discussed in a recent review. 525 8. Impact of SARS-CoV-2 on protein synthesis SARS-CoV-2 contains a positive sense and single-stranded RNA composed of 50 UTR, two large overlapping open reading frames ORF1a and ORF1b, structural and accessory protein genes, and a 30-polyadenylated tail.…”

Section: Interaction Between Nanobodies and Spike Proteinmentioning

confidence: 99%

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

Nguyen,

Lan

et al. 2023

Chem. Soc. Rev.

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“…Recent advances in the coronavirus structure have shown that the surface-exposed portion of the Spike is composed of two subunits: the S1 domain that binds to ACE2 through the receptor binding domain (RBD) and the S2 domain that drives fusion of the viral and host cell membranes. Numbers of VHHs have been identified to target the RBD domain of the Spike protein on the surface of SARS-CoV-2 [113]. Bivalent, bispecific, and trivalent VHHs against the SARS-CoV-2 receptor binding domain are efficient in competing with ACE-2 and demonstrating good therapeutic effects in ex or in vivo experiments [36,58,[114][115][116][117].…”

Section: Nanobody ® Molecules In Infectious and Viral Diseasesmentioning

confidence: 99%

NANOBODY® Molecule, a Giga Medical Tool in Nanodimensions

Kunz,

Durandy,

Seguin

et al. 2023

IJMS

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Although antibodies remain the most widely used tool for biomedical research, antibody technology is not flawless. Innovative alternatives, such as Nanobody® molecules, were developed to address the shortcomings of conventional antibodies. Nanobody® molecules are antigen-binding variable-domain fragments derived from the heavy-chain-only antibodies of camelids (VHH) and combine the advantageous properties of small molecules and monoclonal antibodies. Nanobody® molecules present a small size (~15 kDa, 4 nm long and 2.5 nm wide), high solubility, stability, specificity, and affinity, ease of cloning, and thermal and chemical resistance. Recombinant production in microorganisms is cost-effective, and VHH are also building blocks for multidomain constructs. These unique features led to numerous applications in fundamental research, diagnostics, and therapy. Nanobody® molecules are employed as biomarker probes and, when fused to radioisotopes or fluorophores, represent ideal non-invasive in vivo imaging agents. They can be used as neutralizing agents, receptor-ligand antagonists, or in targeted vehicle-based drug therapy. As early as 2018, the first Nanobody®, Cablivi (caplacizumab), a single-domain antibody (sdAb) drug developed by French pharmaceutical giant Sanofi for the treatment of adult patients with acquired thrombocytopenic purpura (aTTP), was launched. Nanobody® compounds are ideal tools for further development in clinics for diagnostic and therapeutic purposes.

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Nanobodies: COVID-19 and Future Perspectives

Cited by 13 publications

References 169 publications

Nanobodies against SARS-CoV-2 reduced virus load in the brain of challenged mice and neutralized Wuhan, Delta and Omicron Variants

Nanobodies against SARS-CoV-2 reduced virus load in the brain of challenged mice and neutralized Wuhan, Delta and Omicron Variants

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

NANOBODY® Molecule, a Giga Medical Tool in Nanodimensions

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