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

Shigeru FujitaYusuke KosugiIzumi KimuraDaichi Yamasobanull The Genotype To Phenotype Japan G P-Japan ConsortiumKei Sato

Published in: Viruses (2022)

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.

Keyphrases

sars cov
monoclonal antibody
respiratory syndrome coronavirus
copy number
gene expression
dna methylation
single cell
coronavirus disease
transcription factor