Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes

doi:10.1371/journal.pbio.3001209

	Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes
	Fu, Dan 1,2; Zhang, Guangshun 1,2,3,4; Wang, Yuhui 1,2,4; Zhang, Zheng 1,2; Hu, Hengrui 5,6; Shen, Shu 5,7,8; Wu, Jun 3; Li, Bo 1,2,4; Li, Xin 1,2,4,9; Fang, Yaohui 7,8; Liu, Jia 5; Wang, Qiao 10; Zhou, Yunjiao 10; Wang, Wei9 ; Li, Yufeng 5; Lu, Zhonghua 3; Wang, Xiaoxiao 3; Nie, Cui 3; Tian, Yujie 1,2,11; Chen, Da 1,2,4,11; Wang, Yuan 1,2,4,11; Zhou, Xingdong 1,2,4,11; Wang, Qisheng 12; Yu, Feng 12; Zhang, Chen 1,2; Deng, Changjing 3; Zhou, Liang 3; Guan, Guangkuo 3; Shao, Na 3; Lou, Zhiyong 13,14; Deng, Fei 5,7,8; Zhang, Hongkai1,2,9,11 ; Chen, Xinwen 6,15; Wang, Manli 5; Liu, Louis 3; Rao, Zihe1,2,4,9 ; Guo, Yu 1,2,11,15
	2021
发表期刊	PLOS BIOLOGY (IF:7.8[JCR-2023],8.2[5-Year])
ISSN	1544-9173
EISSN	1545-7885
卷号	19 期号:5
DOI	10.1371/journal.pbio.3001209
摘要	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.
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收录类别	SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS类目	Biochemistry & Molecular Biology ; Biology
WOS记录号	WOS:000665464000002
出版者	PUBLIC LIBRARY SCIENCE
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127622
专题	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
通讯作者	Lou, Zhiyong; Deng, Fei; Zhang, Hongkai; Chen, Xinwen; Wang, Manli; Liu, Louis; Rao, Zihe; Guo, Yu
作者单位	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
通讯作者单位	免疫化学研究所
推荐引用方式 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).