Related Experiment Video
Updated: Aug 16, 2025
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab
Shigeru Fujita1,2, Yusuke Kosugi1,2, Izumi Kimura1
1Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.
Abstract:
We have recently revealed that the new SARS-CoV-2 Omicron sublineages BA.4 and BA.5 exhibit increased resistance to cilgavimab, a therapeutic monoclonal antibody, and the resistance to cilgavimab is attributed to the spike L452R substitution. However, it remains unclear how the spike L452R substitution renders resistance to cilgavimab. Here, we demonstrated that the increased resistance to cilgavimab of the spike L452R is possibly caused by the steric hindrance between cilgavimab and its binding interface on the spike. Our results suggest the importance of developing therapeutic antibodies that target SARS-CoV-2 variants harboring the spike L452R substitution.
Insights
New SARS-CoV-2 variants with the spike L452R mutation show resistance to the therapeutic antibody cilgavimab. This resistance is likely due to steric hindrance, necessitating new antibody development for these variants.
Area of Science:
- Virology
- Immunology
- Drug Discovery
Background:
- Recent SARS-CoV-2 Omicron sublineages BA.4 and BA.5 display increased resistance to cilgavimab.
- This resistance is linked to the spike L452R substitution in the virus.
Purpose of the Study:
- To elucidate the mechanism by which the spike L452R substitution confers resistance to cilgavimab.
- To inform the development of novel therapeutic antibodies against SARS-CoV-2 variants.
Main Methods:
- Structural analysis of the interaction between cilgavimab and the SARS-CoV-2 spike protein.
- Investigating the impact of the L452R substitution on antibody binding dynamics.
Main Results:
- The spike L452R substitution is associated with increased resistance to cilgavimab.
- Steric hindrance between cilgavimab and its binding site on the spike protein is the likely cause of resistance.
Conclusions:
- The L452R substitution in SARS-CoV-2 spike protein hinders cilgavimab binding.
- Development of therapeutic antibodies effective against L452R-mutated SARS-CoV-2 variants is crucial.
More Related Videos
06:08Author Spotlight: A Pseudotype Virus System for Assessing Omicron Subvariants and Neutralizing Antibodies in SARS-CoV-2 Research
Published on: September 8, 2023
10:25Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
