Loading...
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.
Bertoglio, Federico Fühner, Viola Ruschig, Maximilian Heine, Philip Alexander Abassi, Leila Klünemann, Thomas Rand, Ulfert Meier, Doris Langreder, Nora Steinke, Stephan
Bertoglio, Federico
Fühner, Viola
Ruschig, Maximilian
Heine, Philip Alexander
Abassi, Leila
Klünemann, Thomas
Rand, Ulfert
Meier, Doris
Langreder, Nora
Steinke, Stephan
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2021-07-07
Submitted date
Files
Loading...
Open Access publication
Adobe PDF, 4.64 MB
Other Titles
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 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.
Citation
Cell Rep. 2021 Jul 27;36(4):109433. doi: 10.1016/j.celrep.2021.109433. Epub 2021 Jul 7.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
EISSN
2211-1247
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution 4.0 International