Journal Article

DZNE-2021-00129

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.

Kreye, J. (First author)DZNE* ; Reincke, S. M.DZNE* ; Kornau, H.-C.DZNE* ; Sanchez Sendin, E.DZNE* ; Corman, V. M.DZNE* ; Liu, H. ; Yuan, M. ; Wu, N. C. ; Zhu, X. ; Lee, C. D. ; Trimpert, J. ; Höltje, M. ; Dietert, K. ; Stöffler, L. ; von Wardenburg, N. ; van Hoof, S. ; Homeyer, M. A. ; Hoffmann, J. ; Abdelgawad, A. ; Gruber, A. D. ; Bertzbach, L. D. ; Vladimirova, D. ; Li, L. Y. ; Barthel, P. C. ; Skriner, K. ; Hocke, A. C. ; Hippenstiel, S. ; Witzenrath, M. ; Suttorp, N. ; Kurth, F. ; Franke, C. ; Endres, M.DZNE* ; Schmitz, D.DZNE* ; Jeworowski, L. M. ; Richter, A. ; Schmidt, M. L. ; Schwarz, T. ; Müller, M. A. ; Drosten, C. ; Wendisch, D. ; Sander, L. E. ; Osterrieder, N. ; Wilson, I. A. ; Prüss, H. (Last author)DZNE*

2020
Elsevier New York, NY

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/j.cell.2020.09.049

Abstract: The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from 10 COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb, CV07-209, neutralized authentic SARS-CoV-2 with an IC50 value of 3.1 ng/mL. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2-neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss, and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.

Keyword(s): Angiotensin-Converting Enzyme 2 (MeSH) ; Animals (MeSH) ; Antibodies, Monoclonal: immunology (MeSH) ; Antibodies, Monoclonal: therapeutic use (MeSH) ; Antibodies, Neutralizing: immunology (MeSH) ; Antibodies, Viral: immunology (MeSH) ; Antibodies, Viral: therapeutic use (MeSH) ; Antigen-Antibody Reactions (MeSH) ; Betacoronavirus: immunology (MeSH) ; Betacoronavirus: metabolism (MeSH) ; Betacoronavirus: pathogenicity (MeSH) ; Binding Sites (MeSH) ; COVID-19 (MeSH) ; Coronavirus Infections: drug therapy (MeSH) ; Coronavirus Infections: pathology (MeSH) ; Coronavirus Infections: virology (MeSH) ; Cricetinae (MeSH) ; Crystallography, X-Ray (MeSH) ; Disease Models, Animal (MeSH) ; Humans (MeSH) ; Kinetics (MeSH) ; Lung: immunology (MeSH) ; Lung: metabolism (MeSH) ; Lung: pathology (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Molecular Dynamics Simulation (MeSH) ; Pandemics (MeSH) ; Peptidyl-Dipeptidase A: chemistry (MeSH) ; Peptidyl-Dipeptidase A: metabolism (MeSH) ; Pneumonia, Viral: drug therapy (MeSH) ; Pneumonia, Viral: pathology (MeSH) ; Pneumonia, Viral: virology (MeSH) ; Protein Binding (MeSH) ; SARS-CoV-2 (MeSH) ; Spike Glycoprotein, Coronavirus: chemistry (MeSH) ; Spike Glycoprotein, Coronavirus: immunology (MeSH) ; Spike Glycoprotein, Coronavirus: metabolism (MeSH) ; COVID-19 ; SARS-CoV-2 ; autoreactivity ; crystal structures ; hamster model ; monoclonal antibody ; neutralizing antibody ; post-exposure ; self-antigens ; self-reactivity ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Peptidyl-Dipeptidase A ; ACE2 protein, human ; Ace2 protein, mouse ; Angiotensin-Converting Enzyme 2

Note: ISSN 0092-8674 not unique: **3 hits**.

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Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)
2. Network Dysfunction (AG Schmitz)
3. Interdisciplinary Dementia Research (AG Endres)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
3. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2020

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Kreye, J.DZNE* ; Reincke, M.DZNE* ; Kornau, H.-C.DZNE* ; Sanchez Sendin, E.DZNE* ; Dietert, K. ; Wilson, I. A. ; Prüß, H.DZNE*
Dataset: A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model. Kreye et al, v1
Mendeley (2020) [10.17632/f6tb3csgjt.1]2020 BibTeX | EndNote: XML, Text | RIS

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