Publikationsdatenbank

A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to most known RBD mutations (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Bertoglio, Federico

Fühner, Viola

Ruschig, Maximilian

Heine, Philip Alexander

Abassi, Leila

Klünemann, Thomas

Rand, Ulfert

Meier, Doris

Langreder, Nora

Steinke, Stephan

Ballmann, Rico

Schneider, Kai-Thomas

Roth, Kristian Daniel Ralph

Kuhn, Philipp

Riese, Peggy

Schäckermann, Dorina

Korn, Janin

Koch, Allan

Chaudhry, M Zeeshan

Eschke, Kathrin

Kim, Yeonsu

Zock-Emmenthal, Susanne

Becker, Marlies

Scholz, Margitta

Moreira, Gustavo Marçal Schmidt Garcia

Wenzel, Esther Veronika

Russo, Giulio

Garritsen, Hendrikus S P

Casu, Sebastian

Gerstner, Andreas

Roth, Günter

Adler, Julia (WE 5)

Trimpert, Jakob (WE 5)

Hermann, Andreas

Schirrmann, Thomas

Dübel, Stefan

Frenzel, André (WE 5)

Van den Heuvel, Joop

Čičin-Šain, Luka

Schubert, Maren

Hust, Michael

Quelle

Cell reports

Bandzählung: 36

Heftzählung: 4

Seiten: Artikel 109433

ISSN: 2211-1247

Sprache

Englisch

Verweise

URL (Volltext): https://www.sciencedirect.com/science/article/pii/S2211124721008500

DOI: 10.1016/j.celrep.2021.109433

Pubmed: 34273271

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

The novel betacoronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes a form of severe pneumonia disease called coronavirus disease 2019 (COVID-19). To develop human neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor-binding domain (RBD) of the spike protein were selected by phage display. The antibody STE90-C11 shows a subnanometer IC50 in a plaque-based live SARS-CoV-2 neutralization assay. The in vivo efficacy of the antibody is demonstrated in the Syrian hamster and in the human angiotensin-converting enzyme 2 (hACE2) mice model. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD is solved at 2.0 Å resolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibition of STE90-C11 is not blocked by many known emerging RBD mutations. STE90-C11-derived human IgG1 with FcγR-silenced Fc (COR-101) is undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19.