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...

Descripción completa

Detalles Bibliográficos
Autores principales: Fujita, Shigeru, Kosugi, Yusuke, Kimura, Izumi, Yamasoba, Daichi, Sato, Kei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Brief Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785715/
https://www.ncbi.nlm.nih.gov/pubmed/36560681
http://dx.doi.org/10.3390/v14122677
_version_ 1784858116185128960
author Fujita, Shigeru
Kosugi, Yusuke
Kimura, Izumi
Yamasoba, Daichi
Sato, Kei
author_facet Fujita, Shigeru
Kosugi, Yusuke
Kimura, Izumi
Yamasoba, Daichi
Sato, Kei
author_sort Fujita, Shigeru
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9785715
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97857152022-12-24 Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab Fujita, Shigeru Kosugi, Yusuke Kimura, Izumi Yamasoba, Daichi Sato, Kei Viruses Brief Report 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. MDPI 2022-11-29 /pmc/articles/PMC9785715/ /pubmed/36560681 http://dx.doi.org/10.3390/v14122677 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Fujita, Shigeru
Kosugi, Yusuke
Kimura, Izumi
Yamasoba, Daichi
Sato, Kei
Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab
title Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab
title_full Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab
title_fullStr Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab
title_full_unstemmed Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab
title_short Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab
title_sort structural insight into the resistance of the sars-cov-2 omicron ba.4 and ba.5 variants to cilgavimab
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785715/
https://www.ncbi.nlm.nih.gov/pubmed/36560681
http://dx.doi.org/10.3390/v14122677
work_keys_str_mv AT fujitashigeru structuralinsightintotheresistanceofthesarscov2omicronba4andba5variantstocilgavimab
AT kosugiyusuke structuralinsightintotheresistanceofthesarscov2omicronba4andba5variantstocilgavimab
AT kimuraizumi structuralinsightintotheresistanceofthesarscov2omicronba4andba5variantstocilgavimab
AT yamasobadaichi structuralinsightintotheresistanceofthesarscov2omicronba4andba5variantstocilgavimab
AT structuralinsightintotheresistanceofthesarscov2omicronba4andba5variantstocilgavimab
AT satokei structuralinsightintotheresistanceofthesarscov2omicronba4andba5variantstocilgavimab

Ejemplares similares