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| Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes | |
Fu, Dan1,2; Zhang, Guangshun1,2,3,4; Wang, Yuhui1,2,4; Zhang, Zheng1,2; Hu, Hengrui5,6; Shen, Shu5,7,8; Wu, Jun3; Li, Bo1,2,4; Li, Xin1,2,4,9; Fang, Yaohui7,8; Liu, Jia5; Wang, Qiao10; Zhou, Yunjiao10; Wang, Wei9  ; Li, Yufeng5; Lu, Zhonghua3; Wang, Xiaoxiao3; Nie, Cui3; Tian, Yujie1,2,11; Chen, Da1,2,4,11; Wang, Yuan1,2,4,11; Zhou, Xingdong1,2,4,11; Wang, Qisheng12; Yu, Feng12; Zhang, Chen1,2; Deng, Changjing3; Zhou, Liang3; Guan, Guangkuo3; Shao, Na3; Lou, Zhiyong13,14; Deng, Fei5,7,8; Zhang, Hongkai1,2,9,11; Chen, Xinwen6,15; Wang, Manli5; Liu, Louis3; Rao, Zihe1,2,4,9; Guo, Yu1,2,11,15
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| 2021 | |
| Source Publication | PLOS BIOLOGY
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| ISSN | 1544-9173 |
| EISSN | 1545-7885 |
| Volume | 19Issue:5 |
| DOI | 10.1371/journal.pbio.3001209 |
| Abstract | The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) threatens global public health and economy unprecedentedly, requiring accelerating development of prophylactic and therapeutic interventions. Molecular understanding of neutralizing antibodies (NAbs) would greatly help advance the development of monoclonal antibody (mAb) therapy, as well as the design of next generation recombinant vaccines. Here, we applied H2L2 transgenic mice encoding the human immunoglobulin variable regions, together with a state-of-the-art antibody discovery platform to immunize and isolate NAbs. From a large panel of isolated antibodies, 25 antibodies showed potent neutralizing activities at sub-nanomolar levels by engaging the spike receptor-binding domain (RBD). Importantly, one human NAb, termed PR1077, from the H2L2 platform and 2 humanized NAb, including PR953 and PR961, were further characterized and subjected for subsequent structural analysis. High-resolution X-ray crystallography structures unveiled novel epitopes on the receptor-binding motif (RBM) for PR1077 and PR953, which directly compete with human angiotensin-converting enzyme 2 (hACE2) for binding, and a novel non-blocking epitope on the neighboring site near RBM for PR961. Moreover, we further tested the antiviral efficiency of PR1077 in the Ad5-hACE2 transduction mouse model of COVID-19. A single injection provided potent protection against SARS-CoV-2 infection in either prophylactic or treatment groups. Taken together, these results shed light on the development of mAb-related therapeutic interventions for COVID-19. |
| URL | 查看原文 |
| Indexed By | SCIE |
| Language | 英语 |
| WOS Research Area | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
| WOS Subject | Biochemistry & Molecular Biology ; Biology |
| WOS ID | WOS:000665464000002 |
| Publisher | PUBLIC LIBRARY SCIENCE |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127622 |
| Collection | 免疫化学研究所_特聘教授组_张宏恺组 免疫化学研究所_特聘教授组_饶子和组 信息科学与技术学院_博士生 免疫化学研究所_公共科研平台_生物医学大数据平台 |
| Corresponding Author | Lou, Zhiyong; Deng, Fei; Zhang, Hongkai; Chen, Xinwen; Wang, Manli; Liu, Louis; Rao, Zihe; Guo, Yu |
| Affiliation | 1.Nankai Univ, State Key Lab Med Chem Biol, Tianjin, Peoples R China; 2.Nankai Univ, Coll Pharm, Tianjin, Peoples R China; 3.Harbour Biomed Suzhou Co Ltd, Suzhou Ind Pk, Suzhou, Peoples R China; 4.Nankai Univ, Coll Life Sci, Tianjin, Peoples R China; 5.Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, Wuhan, Hubei, Peoples R China; 6.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou, Peoples R China; 7.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Hubei, Peoples R China; 8.Chinese Acad Sci, Wuhan Inst Virol, Natl Virus Resource Ctr, Wuhan, Hubei, Peoples R China; 9.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China; 10.Fudan Univ, Key Lab Med Mol Virol MOE NHC CAMS, Sch Basic Med Sci, Shanghai Med Coll, Shanghai, Peoples R China; 11.Nankai Univ, Frontiers Sci Ctr Cell Responses, Tianjin, Peoples R China; 12.Chinese Acad Sci, Shanghai Synchrotron Radiat Facil, Shanghai Adv Res Inst, Shanghai, Peoples R China; 13.Tsinghua Univ, Sch Med, MOE Key Lab Prot Sci, Beijing, Peoples R China; 14.Tsinghua Univ, Sch Med, Collaborat Innovat Ctr Biotherapy, Beijing, Peoples R China; 15.Guangzhou Int Bioisl, Guangzhou Lab, Guangzhou, Guangdong, Peoples R China |
| Corresponding Author Affilication | Shanghai Institute for Advanced Immunochemical Studies |
| Recommended Citation GB/T 7714 | Fu, Dan,Zhang, Guangshun,Wang, Yuhui,et al. Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes[J]. PLOS BIOLOGY,2021,19(5). |
| APA | Fu, Dan.,Zhang, Guangshun.,Wang, Yuhui.,Zhang, Zheng.,Hu, Hengrui.,...&Guo, Yu.(2021).Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes.PLOS BIOLOGY,19(5). |
| MLA | Fu, Dan,et al."Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes".PLOS BIOLOGY 19.5(2021). |
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