Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab
Shigeru Fujita, Yusuke Kosugi, Izumi Kimura, Daichi Yamasoba, Kei Sato
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.
Topics & Concepts
Spike (software development)Monoclonal antibodySteric effectsSpike ProteinSubstitution (logic)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Resistance (ecology)Coronavirus disease 2019 (COVID-19)AntibodyBiologyVirologyChemistryGeneticsStereochemistryMedicineComputer scienceDiseaseProgramming languageInfectious disease (medical specialty)ManagementEconomicsPathologyEcologySARS-CoV-2 and COVID-19 ResearchSARS-CoV-2 detection and testingCOVID-19 Clinical Research Studies