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
Abstract 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 a...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-022-00954-8 |
| _version_ | 1811260531058671616 |
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| author | Xiaofei Wang Ao Hu Xiangyu Chen Yixin Zhang Fei Yu Shuai Yue Arong Li Junsong Zhang Zhiwei Pan Yang Yang Yao Lin Leiqiong Gao Jing Zhou Jing Zhao Fang Li Yaling Shi Feng Huang Xiaofan Yang Yi Peng Luoyang Tu Huan Zhang Huanying Zheng Jun He Hui Zhang Lifan Xu Qizhao Huang Yongqun Zhu Kai Deng Lilin Ye |
| author_facet | Xiaofei Wang Ao Hu Xiangyu Chen Yixin Zhang Fei Yu Shuai Yue Arong Li Junsong Zhang Zhiwei Pan Yang Yang Yao Lin Leiqiong Gao Jing Zhou Jing Zhao Fang Li Yaling Shi Feng Huang Xiaofan Yang Yi Peng Luoyang Tu Huan Zhang Huanying Zheng Jun He Hui Zhang Lifan Xu Qizhao Huang Yongqun Zhu Kai Deng Lilin Ye |
| author_sort | Xiaofei Wang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T18:48:48Z |
| format | Article |
| id | doaj.art-1665f69d1d014c8fabef454695b0d169 |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-04-12T18:48:48Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-1665f69d1d014c8fabef454695b0d1692022-12-22T03:20:32ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352022-04-017111310.1038/s41392-022-00954-8A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBDXiaofei Wang0Ao Hu1Xiangyu Chen2Yixin Zhang3Fei Yu4Shuai Yue5Arong Li6Junsong Zhang7Zhiwei Pan8Yang Yang9Yao Lin10Leiqiong Gao11Jing Zhou12Jing Zhao13Fang Li14Yaling Shi15Feng Huang16Xiaofan Yang17Yi Peng18Luoyang Tu19Huan Zhang20Huanying Zheng21Jun He22Hui Zhang23Lifan Xu24Qizhao Huang25Yongqun Zhu26Kai Deng27Lilin Ye28Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversityInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversitySchool of Laboratory Medicine and Biotechnology, Southern Medical UniversityInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversityInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversityInstitute of Immunology, PLA, Third Military Medical UniversityDepartment of Gastroenterology of the Second Affiliated Hospital School of Medicine, and Life Sciences Institute, Zhejiang UniversityInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversityInstitute of Immunology, PLA, Third Military Medical UniversityInstitute of Immunology, PLA, Third Military Medical UniversityInstitute of Immunology, PLA, Third Military Medical UniversityInstitute of Immunology, PLA, Third Military Medical UniversityInstitute of Immunology, PLA, Third Military Medical UniversityBiomedical Analysis Center, Third Military Medical UniversityGuangzhou Eighth People’s Hospital, Guangzhou Medical UniversityGuangzhou Eighth People’s Hospital, Guangzhou Medical UniversityInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversityInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversityInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversityInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversityGuangdong Provincial Center for Disease Control and PreventionGuangdong Provincial Center for Disease Control and PreventionCenter for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversityInstitute of Immunology, PLA, Third Military Medical UniversitySchool of Laboratory Medicine and Biotechnology, Southern Medical UniversityDepartment of Gastroenterology of the Second Affiliated Hospital School of Medicine, and Life Sciences Institute, Zhejiang UniversityInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen UniversityInstitute of Immunology, PLA, Third Military Medical UniversityAbstract 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.https://doi.org/10.1038/s41392-022-00954-8 |
| spellingShingle | Xiaofei Wang Ao Hu Xiangyu Chen Yixin Zhang Fei Yu Shuai Yue Arong Li Junsong Zhang Zhiwei Pan Yang Yang Yao Lin Leiqiong Gao Jing Zhou Jing Zhao Fang Li Yaling Shi Feng Huang Xiaofan Yang Yi Peng Luoyang Tu Huan Zhang Huanying Zheng Jun He Hui Zhang Lifan Xu Qizhao Huang Yongqun Zhu Kai Deng Lilin Ye 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 Signal Transduction and Targeted Therapy |
| 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 |
| url | https://doi.org/10.1038/s41392-022-00954-8 |
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