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TitleA neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.
Journal, issue, pagesScience, Year 2020
Publish dateJun 22, 2020
AuthorsXiangyang Chi / Renhong Yan / Jun Zhang / Guanying Zhang / Yuanyuan Zhang / Meng Hao / Zhe Zhang / Pengfei Fan / Yunzhu Dong / Yilong Yang / Zhengshan Chen / Yingying Guo / Jinlong Zhang / Yaning Li / Xiaohong Song / Yi Chen / Lu Xia / Ling Fu / Lihua Hou / Junjie Xu / Changming Yu / Jianmin Li / Qiang Zhou / Wei Chen /
PubMed AbstractDeveloping therapeutics against SARS-CoV-2 could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein, but also across the full Spike (S) ...Developing therapeutics against SARS-CoV-2 could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein, but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from ten convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. An mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, but does not bind the RBD. We defined the epitope of 4A8 as the N terminal domain (NTD) of the S protein by determining its cryo-EM structure in complex with the S protein to an overall resolution of 3.1 Angstrom and local resolution of 3.3 Angstrom for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.
External linksPubMed:32571838 / Publisher's page
KeywordsMEMBRANE PROTEIN/IMMUNE SYSTEM / ACE2-B0AT1 complex / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex
MethodsEM (single particle)
Resolution3.1 - 3.3 A
Structure data

EMDB-30276:
cryo EM map of the S protein of SARS-CoV-2 in complex bound with 4A8

EMDB-30277:
Cryo EM map of the interface between NTD of SARS-CoV-2 and 4A8

PDB-7c2l:
S protein of SARS-CoV-2 in complex bound with 4A8

Chemicals

ChemComp-NAG:
Unknown entry

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2

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    • Jacques Dubochet (University of Lausanne, Switzerland) is a pioneer of ice-embedding method of EM specimen (as known as cryo-EM), Most of 3DEM structures in EMDB and PDB are obtained using his method.
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