tetano
Editor, Senior Moderator
Cell Rep
. 2021 Jul 7;109433.
doi: 10.1016/j.celrep.2021.109433. Online ahead of print.
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
Federico Bertoglio[SUP] 1 [/SUP], Viola Fühner[SUP] 1 [/SUP], Maximilian Ruschig[SUP] 1 [/SUP], Philip Alexander Heine[SUP] 1 [/SUP], Leila Abassi[SUP] 2 [/SUP], Thomas Klünemann[SUP] 3 [/SUP], Ulfert Rand[SUP] 2 [/SUP], Doris Meier[SUP] 1 [/SUP], Nora Langreder[SUP] 1 [/SUP], Stephan Steinke[SUP] 1 [/SUP], Rico Ballmann[SUP] 1 [/SUP], Kai-Thomas Schneider[SUP] 1 [/SUP], Kristian Daniel Ralph Roth[SUP] 1 [/SUP], Philipp Kuhn[SUP] 4 [/SUP], Peggy Riese[SUP] 5 [/SUP], Dorina Schäckermann[SUP] 1 [/SUP], Janin Korn[SUP] 1 [/SUP], Allan Koch[SUP] 1 [/SUP], M Zeeshan Chaudhry[SUP] 2 [/SUP], Kathrin Eschke[SUP] 2 [/SUP], Yeonsu Kim[SUP] 2 [/SUP], Susanne Zock-Emmenthal[SUP] 6 [/SUP], Marlies Becker[SUP] 1 [/SUP], Margitta Scholz[SUP] 1 [/SUP], Gustavo Marçal Schmidt Garcia Moreira[SUP] 1 [/SUP], Esther Veronika Wenzel[SUP] 1 [/SUP], Giulio Russo[SUP] 1 [/SUP], Hendrikus S P Garritsen[SUP] 7 [/SUP], Sebastian Casu[SUP] 8 [/SUP], Andreas Gerstner[SUP] 9 [/SUP], Günter Roth[SUP] 10 [/SUP], Julia Adler[SUP] 11 [/SUP], Jakob Trimpert[SUP] 11 [/SUP], Andreas Hermann[SUP] 12 [/SUP], Thomas Schirrmann[SUP] 13 [/SUP], Stefan Dübel[SUP] 1 [/SUP], André Frenzel[SUP] 14 [/SUP], Joop Van den Heuvel[SUP] 3 [/SUP], Luka Čičin-Šain[SUP] 15 [/SUP], Maren Schubert[SUP] 1 [/SUP], Michael Hust[SUP] 16 [/SUP]
Affiliations
Abstract
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 IC[SUB]50[/SUB] 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.
Keywords: RBD; SARS-CoV-2; SARS-CoV-2 variants; coronavirus; immune library; in vivo neutralization; neutralizing antibody; phage display; recombinant antibody; spike protein.
. 2021 Jul 7;109433.
doi: 10.1016/j.celrep.2021.109433. Online ahead of print.
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
Federico Bertoglio[SUP] 1 [/SUP], Viola Fühner[SUP] 1 [/SUP], Maximilian Ruschig[SUP] 1 [/SUP], Philip Alexander Heine[SUP] 1 [/SUP], Leila Abassi[SUP] 2 [/SUP], Thomas Klünemann[SUP] 3 [/SUP], Ulfert Rand[SUP] 2 [/SUP], Doris Meier[SUP] 1 [/SUP], Nora Langreder[SUP] 1 [/SUP], Stephan Steinke[SUP] 1 [/SUP], Rico Ballmann[SUP] 1 [/SUP], Kai-Thomas Schneider[SUP] 1 [/SUP], Kristian Daniel Ralph Roth[SUP] 1 [/SUP], Philipp Kuhn[SUP] 4 [/SUP], Peggy Riese[SUP] 5 [/SUP], Dorina Schäckermann[SUP] 1 [/SUP], Janin Korn[SUP] 1 [/SUP], Allan Koch[SUP] 1 [/SUP], M Zeeshan Chaudhry[SUP] 2 [/SUP], Kathrin Eschke[SUP] 2 [/SUP], Yeonsu Kim[SUP] 2 [/SUP], Susanne Zock-Emmenthal[SUP] 6 [/SUP], Marlies Becker[SUP] 1 [/SUP], Margitta Scholz[SUP] 1 [/SUP], Gustavo Marçal Schmidt Garcia Moreira[SUP] 1 [/SUP], Esther Veronika Wenzel[SUP] 1 [/SUP], Giulio Russo[SUP] 1 [/SUP], Hendrikus S P Garritsen[SUP] 7 [/SUP], Sebastian Casu[SUP] 8 [/SUP], Andreas Gerstner[SUP] 9 [/SUP], Günter Roth[SUP] 10 [/SUP], Julia Adler[SUP] 11 [/SUP], Jakob Trimpert[SUP] 11 [/SUP], Andreas Hermann[SUP] 12 [/SUP], Thomas Schirrmann[SUP] 13 [/SUP], Stefan Dübel[SUP] 1 [/SUP], André Frenzel[SUP] 14 [/SUP], Joop Van den Heuvel[SUP] 3 [/SUP], Luka Čičin-Šain[SUP] 15 [/SUP], Maren Schubert[SUP] 1 [/SUP], Michael Hust[SUP] 16 [/SUP]
Affiliations
- PMID: 34273271
- DOI: 10.1016/j.celrep.2021.109433
Abstract
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 IC[SUB]50[/SUB] 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.
Keywords: RBD; SARS-CoV-2; SARS-CoV-2 variants; coronavirus; immune library; in vivo neutralization; neutralizing antibody; phage display; recombinant antibody; spike protein.