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A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980211/ https://www.ncbi.nlm.nih.gov/pubmed/35383141 http://dx.doi.org/10.1038/s41392-022-00954-8 |
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| author | Wang, Xiaofei Hu, Ao Chen, Xiangyu Zhang, Yixin Yu, Fei Yue, Shuai Li, Arong Zhang, Junsong Pan, Zhiwei Yang, Yang Lin, Yao Gao, Leiqiong Zhou, Jing Zhao, Jing Li, Fang Shi, Yaling Huang, Feng Yang, Xiaofan Peng, Yi Tu, Luoyang Zhang, Huan Zheng, Huanying He, Jun Zhang, Hui Xu, Lifan Huang, Qizhao Zhu, Yongqun Deng, Kai Ye, Lilin |
| author_facet | Wang, Xiaofei Hu, Ao Chen, Xiangyu Zhang, Yixin Yu, Fei Yue, Shuai Li, Arong Zhang, Junsong Pan, Zhiwei Yang, Yang Lin, Yao Gao, Leiqiong Zhou, Jing Zhao, Jing Li, Fang Shi, Yaling Huang, Feng Yang, Xiaofan Peng, Yi Tu, Luoyang Zhang, Huan Zheng, Huanying He, Jun Zhang, Hui Xu, Lifan Huang, Qizhao Zhu, Yongqun Deng, Kai Ye, Lilin |
| author_sort | Wang, Xiaofei |
| collection | PubMed |
| description | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine. |
| format | Online Article Text |
| id | pubmed-8980211 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-89802112022-04-05 A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD Wang, Xiaofei Hu, Ao Chen, Xiangyu Zhang, Yixin Yu, Fei Yue, Shuai Li, Arong Zhang, Junsong Pan, Zhiwei Yang, Yang Lin, Yao Gao, Leiqiong Zhou, Jing Zhao, Jing Li, Fang Shi, Yaling Huang, Feng Yang, Xiaofan Peng, Yi Tu, Luoyang Zhang, Huan Zheng, Huanying He, Jun Zhang, Hui Xu, Lifan Huang, Qizhao Zhu, Yongqun Deng, Kai Ye, Lilin Signal Transduct Target Ther Article The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine. Nature Publishing Group UK 2022-04-05 /pmc/articles/PMC8980211/ /pubmed/35383141 http://dx.doi.org/10.1038/s41392-022-00954-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Wang, Xiaofei Hu, Ao Chen, Xiangyu Zhang, Yixin Yu, Fei Yue, Shuai Li, Arong Zhang, Junsong Pan, Zhiwei Yang, Yang Lin, Yao Gao, Leiqiong Zhou, Jing Zhao, Jing Li, Fang Shi, Yaling Huang, Feng Yang, Xiaofan Peng, Yi Tu, Luoyang Zhang, Huan Zheng, Huanying He, Jun Zhang, Hui Xu, Lifan Huang, Qizhao Zhu, Yongqun Deng, Kai Ye, Lilin A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD |
| title | A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD |
| title_full | A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD |
| title_fullStr | A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD |
| title_full_unstemmed | A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD |
| title_short | A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD |
| title_sort | potent human monoclonal antibody with pan-neutralizing activities directly dislocates s trimer of sars-cov-2 through binding both up and down forms of rbd |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980211/ https://www.ncbi.nlm.nih.gov/pubmed/35383141 http://dx.doi.org/10.1038/s41392-022-00954-8 |
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