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Updated: Oct 28, 2025
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to
Federico Bertoglio1, Viola Fühner1, Maximilian Ruschig1
1Technische Universität Braunschweig, Institut für Biochemie, Biotechnologie und Bioinformatik, Abteilung Biotechnologie, Spielmannstr. 7, 38106 Braunschweig, Germany.
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.
Insights
Researchers developed a potent neutralizing antibody, STE90-C11, targeting the SARS-CoV-2 receptor-binding domain. This antibody demonstrated in vivo efficacy and is advancing to clinical trials for treating COVID-19.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes COVID-19, a significant global health concern.
- Development of effective neutralizing antibodies is crucial for combating SARS-CoV-2 infections.
Purpose of the Study:
- To generate and characterize human neutralizing antibodies against the SARS-CoV-2 receptor-binding domain (RBD).
- To evaluate the therapeutic potential of a lead antibody candidate, STE90-C11, in preclinical models and assess its mechanism of action.
Main Methods:
- Construction of antibody gene libraries from convalescent COVID-19 patients.
- Selection of recombinant antibody fragments (scFv) targeting SARS-CoV-2 RBD using phage display.
- In vitro neutralization assays, in vivo efficacy studies in Syrian hamsters and hACE2 mice models, and crystal structure determination of antibody-RBD complex.
Main Results:
- The antibody STE90-C11 exhibited potent neutralization with a subnanometer IC50 in live virus assays.
- STE90-C11 demonstrated significant in vivo efficacy in relevant animal models.
- Structural analysis revealed that STE90-C11 binds to the ACE2 binding site on the RBD and is effective against emerging RBD mutations.
- A human IgG1 derivative, COR-101, is currently in Phase Ib/II clinical trials.
Conclusions:
- STE90-C11 is a highly effective neutralizing antibody against SARS-CoV-2 with a well-defined mechanism of action.
- The antibody's efficacy in preclinical models and its broad activity against RBD mutations support its therapeutic potential.
- Clinical development of COR-101 indicates promising prospects for treating moderate to severe COVID-19.
