Nanobody derived using a peptide epitope from the spike protein receptor-binding motif inhibits entry of SARS-CoV-2 variants

Mendon, Nivya; Ganie, Rayees; Kesarwani, Shubham; Dileep, Drisya; Sasi, Sarika; Lama, Prakash; Chandra, Anchal; Sirajuddin, Minhajuddin

doi:10.1016/j.jbc.2022.102732

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…Approaches to rapidly generate novel potent antibodies effective against emerging viral variants for clinical use, e.g . chimaeric antibodies 95 , broadly neutralizing antibodies 96 and nanobodies 97 - 99 , require prioritization.…”

Section: Discussionmentioning

confidence: 99%

Overview of immunological & virological factors driving the evolution & global spread of SARS-CoV-2 variants

Ramasamy

2023

Indian J Med Res

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The SARS-CoV-2, a highly infectious positive strand RNA virus first identified in December 2019, has produced multiple genetic variants that have rapidly and sequentially spread worldwide during the coronavirus disease 2019 (COVID-19) pandemic. Genetic changes in SARS-CoV-2 for greater infectivity, replication and transmission were selected during the early stages of the pandemic. More recently, after widespread infection and vaccination, SARS-CoV-2 variants that evade antigen-specific adaptive immunity, have begun to be selected. This article provides an overview of the molecular immunological and virological factors underlying the origin and global spread of important SARS-CoV-2 variant lineages.

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Section: Discussionmentioning

confidence: 99%

Overview of immunological & virological factors driving the evolution & global spread of SARS-CoV-2 variants

Ramasamy

2023

Indian J Med Res

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“…C57BL/6 mice with six weeks of age were immunized with one of 19 selected RAD-SCoV-epitopes. The immunization regime consisted of three doses of 10 μg of each protein and 1 μg of the non-toxic heat-labile toxin-1 as an adjuvant, administered at 1st, 14th and 28th days 33 . 14 days after the last immunization, peripheral blood samples were collected via the submandibular plexus.…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 Spike protein peptides displayed in the Pyrococcus furiosus RAD system preserve epitopes antigenicity, immunogenicity, and virus-neutralizing activity of antibodies

Cioffi,

de Castro-Amarante,

Lulla

et al. 2023

Sci Rep

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Amongst the potential contribution of protein or peptide-display systems to study epitopes with relevant immunological features, the RAD display system stands out as a highly stable scaffold protein that allows the presentation of constrained target peptides. Here, we employed the RAD display system to present peptides derived from the SARS-CoV-2 Spike (S) protein as a tool to detect specific serum antibodies and to generate polyclonal antibodies capable of inhibiting SARS-CoV-2 infectivity in vitro. 44 linear S-derived peptides were genetically fused with the RAD scaffold (RAD-SCoV-epitopes) and screened for antigenicity with sera collected from COVID-19-infected patients. In a second step, selected RAD-SCoV-epitopes were used to immunize mice and generate antibodies. Phenotypic screening showed that some of these antibodies were able to recognize replicating viral particles in VERO CCL-81 and most notably seven of the RAD-SCoV-epitopes were able to induce antibodies that inhibited viral infection. Our findings highlight the RAD display system as an useful platform for the immunological characterization of peptides and a potentially valuable strategy for the design of antigens for peptide-based vaccines, for epitope-specific antibody mapping, and for the development of antibodies for diagnostic and therapeutic purposes.

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“…Other nanobodies can be generated by using short peptide sequences from the RBD or S protein as epitopes. For example, a 9-amino acid peptide from the RBD (residues 486-494 of S protein) was used to identify nanobody N1.2, which blocks SARS-CoV-2 S protein-mediated pseudovirus entry; the bivalent version of this nanobody shows improved neutralizing activity against the pseudotyped SARS-CoV-2 original strain and the Omicron-BA1 variant [102].…”

Section: Antigens For Screening Nanobodiesmentioning

confidence: 99%

Therapeutic nanobodies against SARS-CoV-2 and other pathogenic human coronaviruses

Yang,

Li,

2024

J Nanobiotechnol

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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 have been arisen as an effective research tool for development of nanobiotechnologies with a variety of applications. Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, have caused serious outbreaks or a global pandemic, and continue to post a threat to public health worldwide. The viral spike (S) protein and its cognate receptor-binding domain (RBD), which initiate viral entry and play a critical role in virus pathogenesis, are important therapeutic targets. This review describes pathogenic human CoVs, including viral structures and proteins, and S protein-mediated viral entry process. It also summarizes recent advances in development of nanobodies targeting these CoVs, focusing on those targeting the S protein and RBD. Finally, we discuss potential strategies to improve the efficacy of nanobodies against emerging SARS-CoV-2 variants and other CoVs with pandemic potential. It will provide important information for rational design and evaluation of therapeutic agents against emerging and reemerging pathogens. Graphical abstract

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Nanobody derived using a peptide epitope from the spike protein receptor-binding motif inhibits entry of SARS-CoV-2 variants

Cited by 6 publications

References 49 publications

Overview of immunological & virological factors driving the evolution & global spread of SARS-CoV-2 variants

Overview of immunological & virological factors driving the evolution & global spread of SARS-CoV-2 variants

SARS-CoV-2 Spike protein peptides displayed in the Pyrococcus furiosus RAD system preserve epitopes antigenicity, immunogenicity, and virus-neutralizing activity of antibodies

Therapeutic nanobodies against SARS-CoV-2 and other pathogenic human coronaviruses

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