A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5
Abstract The global spread of Severe Acute Respiratory Syndrome Coronavirus 2. (SARS-CoV-2) and its variant strains, including Alpha, Beta, Gamma, Delta, and now Omicron, pose a significant challenge. With the constant evolution of the virus, Omicron and its subtypes BA.1, BA.2, BA.3, BA.4, and BA.5...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-024-02114-6 |
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| author | Zhe Chen Leilei Feng Lei Wang Li Zhang Binyang Zheng Hua Fu Fengdi Li Ligai Liu Qi Lv Ran Deng YanLi Xu Yongfeng Hu Jianhua Zheng Chuan Qin Linlin Bao Xiangxi Wang Qi Jin |
| author_facet | Zhe Chen Leilei Feng Lei Wang Li Zhang Binyang Zheng Hua Fu Fengdi Li Ligai Liu Qi Lv Ran Deng YanLi Xu Yongfeng Hu Jianhua Zheng Chuan Qin Linlin Bao Xiangxi Wang Qi Jin |
| author_sort | Zhe Chen |
| collection | DOAJ |
| description | Abstract The global spread of Severe Acute Respiratory Syndrome Coronavirus 2. (SARS-CoV-2) and its variant strains, including Alpha, Beta, Gamma, Delta, and now Omicron, pose a significant challenge. With the constant evolution of the virus, Omicron and its subtypes BA.1, BA.2, BA.3, BA.4, and BA.5 have developed the capacity to evade neutralization induced by previous vaccination or infection. This evasion highlights the urgency in discovering new monoclonal antibodies (mAbs) with neutralizing activity, especially broadly neutralizing antibodies (bnAbs), to combat the virus.In the current study, we introduced a fully human neutralizing mAb, CR9, that targets Omicron variants. We demonstrated the mAb’s effectiveness in inhibiting Omicron replication both in vitro and in vivo. Structural analysis using cryo-electron microscopy (cryo-EM) revealed that CR9 binds to an epitope formed by RBD residues, providing a molecular understanding of its neutralization mechanism. Given its potency and specificity, CR9 holds promise as a potential adjunct therapy for treating Omicron infections. Our findings highlight the importance of continuous mAb discovery and characterization in addressing the evolving threat of COVID-19. |
| format | Article |
| id | doaj-art-19b660278d664e229c2725475f11c977 |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-19b660278d664e229c2725475f11c9772025-01-19T12:40:24ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-01-011011810.1038/s41392-024-02114-6A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5Zhe Chen0Leilei Feng1Lei Wang2Li Zhang3Binyang Zheng4Hua Fu5Fengdi Li6Ligai Liu7Qi Lv8Ran Deng9YanLi Xu10Yongfeng Hu11Jianhua Zheng12Chuan Qin13Linlin Bao14Xiangxi Wang15Qi Jin16NHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences & Peking Union Medical CollegeCAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of SciencesCAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of SciencesDepartment of Vaccine Clinical Evaluation, Jiangsu Provincial Center for Disease Prevention and ControlDepartment of Vaccine Clinical Evaluation, Jiangsu Provincial Center for Disease Prevention and ControlNHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of HealthBeijing Ditan Hospital, Capital Medical UniversityInstitute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of HealthInstitute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of HealthChronic Disease Management Center, Beijing Ditan Hospital, Capital Medical UniversityNHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences & Peking Union Medical CollegeNHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInstitute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of HealthInstitute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of HealthCAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of SciencesNHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences & Peking Union Medical CollegeAbstract The global spread of Severe Acute Respiratory Syndrome Coronavirus 2. (SARS-CoV-2) and its variant strains, including Alpha, Beta, Gamma, Delta, and now Omicron, pose a significant challenge. With the constant evolution of the virus, Omicron and its subtypes BA.1, BA.2, BA.3, BA.4, and BA.5 have developed the capacity to evade neutralization induced by previous vaccination or infection. This evasion highlights the urgency in discovering new monoclonal antibodies (mAbs) with neutralizing activity, especially broadly neutralizing antibodies (bnAbs), to combat the virus.In the current study, we introduced a fully human neutralizing mAb, CR9, that targets Omicron variants. We demonstrated the mAb’s effectiveness in inhibiting Omicron replication both in vitro and in vivo. Structural analysis using cryo-electron microscopy (cryo-EM) revealed that CR9 binds to an epitope formed by RBD residues, providing a molecular understanding of its neutralization mechanism. Given its potency and specificity, CR9 holds promise as a potential adjunct therapy for treating Omicron infections. Our findings highlight the importance of continuous mAb discovery and characterization in addressing the evolving threat of COVID-19.https://doi.org/10.1038/s41392-024-02114-6 |
| spellingShingle | Zhe Chen Leilei Feng Lei Wang Li Zhang Binyang Zheng Hua Fu Fengdi Li Ligai Liu Qi Lv Ran Deng YanLi Xu Yongfeng Hu Jianhua Zheng Chuan Qin Linlin Bao Xiangxi Wang Qi Jin A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 Signal Transduction and Targeted Therapy |
| title | A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 |
| title_full | A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 |
| title_fullStr | A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 |
| title_full_unstemmed | A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 |
| title_short | A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 |
| title_sort | broadly neutralizing antibody against the sars cov 2 omicron sub variants ba 1 ba 2 ba 2 12 1 ba 4 and ba 5 |
| url | https://doi.org/10.1038/s41392-024-02114-6 |
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