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LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants
Kathryn Westendorf1, Stefanie Žentelis1, Lingshu Wang2
1AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
Cell Reports
|May 14, 2022
Summary
A new antibody, LY-CoV1404 (bebtelovimab), effectively neutralizes SARS-CoV-2 variants, including Omicron. Its conserved binding epitope suggests it could be a vital therapeutic for COVID-19, even with emerging mutations.
Area of Science:
- Virology
- Immunology
- Drug Discovery
Background:
- Monoclonal antibodies (mAbs) targeting SARS-CoV-2 reduce COVID-19 hospitalization risk.
- Emerging SARS-CoV-2 variants of concern (VOCs) impact the efficacy of existing therapeutic mAbs.
- Development of broadly neutralizing antibodies is crucial for sustained therapeutic options.
Purpose of the Study:
- To isolate and characterize a novel SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody with broad neutralizing activity.
- To evaluate the neutralization potency of the isolated antibody against authentic SARS-CoV-2 and its variants.
- To assess the structural basis for the antibody's broad activity and its potential as a therapeutic agent.
Main Methods:
- High-throughput B cell screening to isolate SARS-CoV-2 neutralizing monoclonal antibodies (mAbs).
- Pseudovirus and authentic virus neutralization assays against various SARS-CoV-2 strains and variants.
- Structural analysis of the antibody-epitope interaction to understand binding conservation.
Main Results:
- LY-CoV1404 (bebtelovimab) was identified as a potent SARS-CoV-2 RBD-specific antibody.
- LY-CoV1404 demonstrated potent neutralization of authentic SARS-CoV-2 and multiple VOCs, including B.1.1.7, B.1.351, B.1.617.2, and Omicron (B.1.1.529) and its subvariant BA.2.
- Structural analysis indicated a conserved epitope, with activity unaffected by common mutations like N501Y and N439K.
Conclusions:
- LY-CoV1404 exhibits broad and potent neutralization against a wide range of SARS-CoV-2 variants.
- The conserved epitope of LY-CoV1404 suggests sustained efficacy against current and potentially future SARS-CoV-2 variants.
- LY-CoV1404 represents a promising therapeutic candidate for the treatment of COVID-19 across diverse viral strains.
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