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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/12/2677 |
| _version_ | 1797454993013342208 |
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| author | Shigeru Fujita Yusuke Kosugi Izumi Kimura Daichi Yamasoba The Genotype to Phenotype Japan (G2P-Japan) Consortium Kei Sato |
| author_facet | Shigeru Fujita Yusuke Kosugi Izumi Kimura Daichi Yamasoba The Genotype to Phenotype Japan (G2P-Japan) Consortium Kei Sato |
| author_sort | Shigeru Fujita |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T15:45:08Z |
| format | Article |
| id | doaj.art-c69842851b254caca2b4771ce97b5849 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T15:45:08Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-c69842851b254caca2b4771ce97b58492023-11-24T18:37:41ZengMDPI AGViruses1999-49152022-11-011412267710.3390/v14122677Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to CilgavimabShigeru Fujita0Yusuke Kosugi1Izumi Kimura2Daichi Yamasoba3The Genotype to Phenotype Japan (G2P-Japan) ConsortiumKei Sato4Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, JapanDivision of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, JapanDivision of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, JapanDivision of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, JapanDivision of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, JapanWe 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.https://www.mdpi.com/1999-4915/14/12/2677SARS-CoV-2COVID-19OmicronBA.4BA.5cilgavimab |
| spellingShingle | Shigeru Fujita Yusuke Kosugi Izumi Kimura Daichi Yamasoba The Genotype to Phenotype Japan (G2P-Japan) Consortium Kei Sato Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab Viruses SARS-CoV-2 COVID-19 Omicron BA.4 BA.5 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 | SARS-CoV-2 COVID-19 Omicron BA.4 BA.5 cilgavimab |
| url | https://www.mdpi.com/1999-4915/14/12/2677 |
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