Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab

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 substitut...

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Bibliographic Details
Main Authors: Shigeru Fujita, Yusuke Kosugi, Izumi Kimura, Daichi Yamasoba, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Kei Sato
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/14/12/2677
Description
Summary: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.
ISSN:1999-4915