Structural and functional characterization of nanobodies that neutralize Omicron variants of SARS-CoV-2-Reference-Cited by-同舟云学术

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

Published:2024-06 Issue:6 Volume:14 Page:
ISSN:2046-2441
Container-title:Open Biology
language:en
Short-container-title:Open Biol.

Author:

Cornish Katy¹,Huo Jiandong¹²,Jones Luke³⁴,Sharma Parul⁵,Thrush Joseph W.¹^ORCID,Abdelkarim Sahar¹,Kipar Anja⁵⁶,Ramadurai Siva¹,Weckener Miriam¹,Mikolajek Halina⁷,Liu Sai⁸,Buckle Imogen¹,Bentley Eleanor⁵,Kirby Adam⁵,Han Ximeng⁵,Laidlaw Stephen M.³⁴,Hill Michelle⁸,Eyssen Lauren¹,Norman Chelsea¹,Le Bas Audrey¹^ORCID,Clarke John¹^ORCID,James William⁸,Stewart James P.⁵^ORCID,Carroll Miles³⁴,Naismith James H.¹²,Owens Raymond J.¹²^ORCID

Affiliation:

1. Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK

2. Division of Structural Biology, Nuffield Department of Medicine, University of Oxford , Oxford, UK

3. Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford , Oxford, UK

4. Wellcome Centre for Human Genetics, University of Oxford , Oxford, UK

5. Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK

6. Vetsuisse Faculty, Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, University of Zurich , Zurich, Switzerland

7. Diamond Light Source Ltd, Harwell Science Campus , Didcot, UK

8. James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford , Oxford, UK

Abstract

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.

Funder

US Food and Drug Administration

the Histology Laboratory, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich

Diamond Light Source

EPSRC, Wellcome Trust

BBSRC

Reading University

Rosalind Franklin University

Publisher

The Royal Society

Link

https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.230252

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