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Structural and functional characterization of nanobodies that neutralize Omicron variants of SARS-CoV-2.

التفاصيل البيبلوغرافية
العنوان: Structural and functional characterization of nanobodies that neutralize Omicron variants of SARS-CoV-2.
المؤلفون: Cornish K; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK., Huo J; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK.; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford , Oxford, UK., Jones L; Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford , Oxford, UK.; Wellcome Centre for Human Genetics, University of Oxford , Oxford, UK., Sharma P; Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK., Thrush JW; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK., Abdelkarim S; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK., Kipar A; Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK.; Vetsuisse Faculty, Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, University of Zurich , Zurich, Switzerland., Ramadurai S; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK., Weckener M; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK., Mikolajek H; Diamond Light Source Ltd, Harwell Science Campus , Didcot, UK., Liu S; James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford , Oxford, UK., Buckle I; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK., Bentley E; Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK., Kirby A; Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK., Han X; Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK., Laidlaw SM; Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford , Oxford, UK.; Wellcome Centre for Human Genetics, University of Oxford , Oxford, UK., Hill M; James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford , Oxford, UK., Eyssen L; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK., Norman C; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK., Le Bas A; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK., Clarke J; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK., James W; James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford , Oxford, UK., Stewart JP; Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK., Carroll M; Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford , Oxford, UK.; Wellcome Centre for Human Genetics, University of Oxford , Oxford, UK., Naismith JH; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK.; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford , Oxford, UK., Owens RJ; Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK.; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford , Oxford, UK.
المصدر: Open biology [Open Biol] 2024 Jun; Vol. 14 (6), pp. 230252. Date of Electronic Publication: 2024 Jun 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Royal Society Pub Country of Publication: England NLM ID: 101580419 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2046-2441 (Electronic) Linking ISSN: 20462441 NLM ISO Abbreviation: Open Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Royal Society Pub., [2011]-
مواضيع طبية MeSH: SARS-CoV-2*/immunology , Single-Domain Antibodies*/immunology , Single-Domain Antibodies*/chemistry , Single-Domain Antibodies*/pharmacology , Antibodies, Neutralizing*/immunology , Antibodies, Neutralizing*/chemistry , COVID-19*/immunology , COVID-19*/virology , Spike Glycoprotein, Coronavirus*/immunology , Spike Glycoprotein, Coronavirus*/chemistry , Spike Glycoprotein, Coronavirus*/metabolism , Spike Glycoprotein, Coronavirus*/genetics , Antibodies, Viral*/immunology, Animals ; Humans ; Camelids, New World/immunology ; Epitopes/immunology ; Epitopes/chemistry ; Cricetinae ; Protein Binding ; Models, Molecular
مستخلص: The Omicron strains of SARS-CoV-2 pose a significant challenge to the development of effective antibody-based treatments as immune evasion has compromised most available immune therapeutics. Therefore, in the 'arms race' with the virus, there is a continuing need to identify new biologics for the prevention or treatment of SARS-CoV-2 infections. Here, we report the isolation of nanobodies that bind to the Omicron BA.1 spike protein by screening nanobody phage display libraries previously generated from llamas immunized with either the Wuhan or Beta spike proteins. The structure and binding properties of three of these nanobodies (A8, H6 and B5-5) have been characterized in detail providing insight into their binding epitopes on the Omicron spike protein. Trimeric versions of H6 and B5-5 neutralized the SARS-CoV-2 variant of concern BA.5 both in vitro and in the hamster model of COVID-19 following nasal administration. Thus, either alone or in combination could serve as starting points for the development of new anti-viral immunotherapeutics.
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معلومات مُعتمدة: Diamond Light Source; Reading University; the Histology Laboratory, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich; EM; BBSRC; United Kingdom WT_ Wellcome Trust; US Food and Drug Administration; EPSRC, Wellcome Trust; Rosalind Franklin University
فهرسة مساهمة: Keywords: COVID-19; Omicrons; SARS-CoV-2; nanobodies; spike protein
المشرفين على المادة: 0 (Single-Domain Antibodies)
0 (Antibodies, Neutralizing)
0 (Spike Glycoprotein, Coronavirus)
0 (Antibodies, Viral)
0 (spike protein, SARS-CoV-2)
0 (Epitopes)
SCR Organism: SARS-CoV-2 variants
تواريخ الأحداث: Date Created: 20240605 Date Completed: 20240605 Latest Revision: 20240731
رمز التحديث: 20240731
مُعرف محوري في PubMed: PMC11285730
DOI: 10.1098/rsob.230252
PMID: 38835241
قاعدة البيانات: MEDLINE
الوصف
تدمد:2046-2441
DOI:10.1098/rsob.230252