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Structure basis of two nanobodies neutralizing SARS-CoV-2 Omicron variant by targeting ultra-conservative epitopes

文献类型：期刊论文

作者Sun, Zengchao1,2; Wang, Lu2; Li, Lingyun2,3; Sun, Yili11; Zhang, Daizhou10; Zhou, Siyu2,3; Li, Yuying2; Li, Xiyang2; Qiao, Huarui2; Cui, Qianqian2
刊名JOURNAL OF STRUCTURAL BIOLOGY
出版日期2023-09-01
卷号215期号:3页码:9
ISSN号1047-8477
关键词SARS-CoV-2 virus Receptor -binding domain Nanobody Crystal structure Conservative binding epitope Bi-paratopic nanobodies
DOI10.1016/j.jsb.2023.107996
通讯作者Meng, Xiangjing(fredamxj@163.com) ; Xu, Jianfeng(jfxu@shou.edu.cn) ; Geng, Yong(gengyong@simm.ac.cn) ; Dai, Yuanyuan(daiyuanyuan@cicams.ac.cn)
英文摘要The evolving SARS-CoV-2 Omicron strain has repeatedly caused widespread disease epidemics, and effective antibody drugs continue to be in short supply. Here, we identified a batch of nanobodies with high affinity for receptor binding domain (RBD) of SARS-CoV-2 spike protein, separated them into three classes using high performance liquid chromatography (HPLC), and then resolved the crystal structure of the ternary complexes of two non-competing nanobodies (NB1C6 and NB1B5) with RBD using X-ray crystallography. The structures showed that NB1B5 and NB1C6 bind to the left and right flank of the RBD, respectively, and that the binding epitopes are highly conserved cryptic sites in all SARS-CoV-2 mutant strains, as well as that NB1B5 can effectively block the ACE2. These two nanobodies were covalently linked into multivalent and bi-paratopic formats, and have a high affinity and neutralization potency for omicron, potentially inhibiting viral escape. The binding sites of these two nanobodies are relatively conserved, which help guide the structural design of antibodies targeting future variants of SARS-CoV-2 to combat COVID-19 epidemics and pandemics.
WOS关键词PROTEIN ; DOMAIN ; SITE
资助项目National Natural Science Foundation of China[31670743] ; Strategic Priority Research Program of the Chi- nese Academy of Sciences[XDA12040326] ; Science and Technology Commission of Shanghai Municipality[18JC1415400] ; Joint Research Fund for Overseas, Hong Kong and Macao Scholars[81628013] ; Natural Science Foundation of Shanghai[16ZR1442900] ; National Science Foundation for Young Scholar projects[81803599] ; Zhejiang University COVID-19 Special Project[2020XGZX092] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[CASIMM0120164013] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM1606YZZ-06] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM1601KF-06] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[55201631121116101] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[55201631121108000] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[5112345601] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[2015123456005] ; Jinan Innovation Team Project[202228051]
WOS研究方向Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
语种英语
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号WOS:001044947800001
源URL[http://119.78.100.183/handle/2S10ELR8/306890]  
专题新药研究国家重点实验室
通讯作者Meng, Xiangjing; Xu, Jianfeng; Geng, Yong; Dai, Yuanyuan
作者单位1.Shanghai Ocean Univ, Coll Food Sci & Technol, Dept Biopharmaceut, Shanghai 201306, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Med Sci, Natl Canc Ctr, Dept Pharm, Beijing 100021, Peoples R China
5.Chinese Acad Med Sci, Natl Clin Res Ctr Canc, Beijing 100021, Peoples R China
6.Chinese Acad Med Sci, Canc Hosp, Beijing 100021, Peoples R China
7.Peking Union Med Coll, Beijing 100021, Peoples R China
8.Chinese Acad Med Sci Langfang Campus, Canc Hosp, Natl Canc Ctr, Langfang 065001, Peoples R China
9.Chinese Acad Med Sci Langfang Campus, Canc Hosp, Natl Clin Res Ctr Canc, Langfang 065001, Peoples R China
10.Shandong Acad Pharmaceut Sci, Shandong Prov Key Lab Biopharmaceut, Jinan 250101, Peoples R China
推荐引用方式
GB/T 7714		 Sun, Zengchao,Wang, Lu,Li, Lingyun,et al. Structure basis of two nanobodies neutralizing SARS-CoV-2 Omicron variant by targeting ultra-conservative epitopes[J]. JOURNAL OF STRUCTURAL BIOLOGY,2023,215(3):9.
APA Sun, Zengchao.,Wang, Lu.,Li, Lingyun.,Sun, Yili.,Zhang, Daizhou.,...&Dai, Yuanyuan.(2023).Structure basis of two nanobodies neutralizing SARS-CoV-2 Omicron variant by targeting ultra-conservative epitopes.JOURNAL OF STRUCTURAL BIOLOGY,215(3),9.
MLA Sun, Zengchao,et al."Structure basis of two nanobodies neutralizing SARS-CoV-2 Omicron variant by targeting ultra-conservative epitopes".JOURNAL OF STRUCTURAL BIOLOGY 215.3(2023):9.

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来源：上海药物研究所

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