A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2

Science
Xiangyang ChiWei Chen

Abstract

Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (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 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One 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 with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.

References

Jul 1, 1987·Molecular Biology and Evolution·N Saitou, M Nei
Feb 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·W J Wilbur, D J Lipman
Jan 1, 1994·The Journal of Experimental Medicine·E P RockY H Chien
Feb 13, 2001·Virology·T M Gallagher, M J Buchmeier
Apr 12, 2003·The New England Journal of Medicine·Thomas G KsiazekUNKNOWN SARS Working Group
Dec 17, 2003·Cell·Dimiter S Dimitrov
Jul 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·Koichiro TamuraSudhir Kumar
Nov 19, 2004·Cellular and Molecular Life Sciences : CMLS·J H KuhnM Farzan
Sep 17, 2008·Current Protocols in Bioinformatics·Julie D ThompsonDes G Higgins
Feb 28, 2009·Nature Protocols·Kenneth SmithPatrick C Wilson
Mar 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sandrine BelouzardGary R Whittaker
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Jun 3, 2011·Cold Spring Harbor Protocols·Véronique GiudicelliMarie-Paule Lefranc
Nov 22, 2011·Journal of Molecular Biology·Sjors H W Scheres
Sep 25, 2012·Journal of Structural Biology·Sjors H W Scheres
Oct 19, 2012·The New England Journal of Medicine·Ali M ZakiRon A M Fouchier
May 15, 2013·Nucleic Acids Research·Jian YeJames M Ostell
Jun 13, 2015·Bioinformatics·Namita T GuptaSteven H Kleinstein
Nov 26, 2015·Journal of Structural Biology·Kai Zhang
Mar 24, 2016·Molecular Biology and Evolution·Sudhir KumarKoichiro Tamura
Feb 7, 2017·Nature Methods·Ali PunjaniMarcus A Brubaker
Jun 7, 2019·Emerging Microbes & Infections·Jiuyang XuLinqi Zhang
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Feb 23, 2020·Science·Daniel WrappJason S McLellan

❮ Previous
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Citations

Sep 18, 2020·Expert Opinion on Therapeutic Targets·Shibo JiangLanying Du
Sep 9, 2020·Expert Review of Clinical Pharmacology·Leilei AiQiaojun He
Aug 13, 2020·Nature Reviews. Cancer·Anna Dart
Aug 28, 2020·Frontiers in Molecular Biosciences·Luciano PironeEmilia Pedone
Aug 2, 2020·Nature Structural & Molecular Biology·Xiaoli XiongJohn A G Briggs
Sep 11, 2020·The Journal of Experimental Medicine·Ting ZhouJun Wang
Sep 24, 2020·Signal Transduction and Targeted Therapy·Fei YuShibo Jiang
Sep 29, 2020·Frontiers in Immunology·Anna PomésMaksymilian Chruszcz
Sep 30, 2020·Proceedings of the National Academy of Sciences of the United States of America·Mary Hongying ChengIvet Bahar
Sep 9, 2020·Cellular & Molecular Immunology·Yang LiSheng-Ce Tao
May 22, 2020·European Journal of Immunology·Huibin LvChris K P Mok
Oct 13, 2020·Emerging Microbes & Infections·Benjamin MeyerChantal Reusken
Oct 13, 2020·Frontiers in Microbiology·Yuki Furuse, Hitoshi Oshitani
Oct 21, 2020·Nature Reviews. Nephrology·Luca PericoGiuseppe Remuzzi
Oct 23, 2020·F1000Research·John L CanigliaKiran K Velpula
Oct 27, 2020·Journal of Computer-aided Molecular Design·Giuseppe DeganuttiChristopher A Reynolds
Oct 13, 2020·Nature·Christopher O BarnesPamela J Bjorkman
Nov 8, 2020·Science·Kevin W NgGeorge Kassiotis
Nov 11, 2020·Biochemical Society Transactions·Jiayue-Clara Jiang, Yan Zhang
Nov 28, 2020·Nature Metabolism·Congwen WeiHui Zhong
Nov 25, 2020·Current Opinion in HIV and AIDS·Pilar MendozaChristian Gaebler
Dec 9, 2020·Science Translational Medicine·Zijun WangMichel C Nussenzweig
Nov 19, 2020·Transboundary and Emerging Diseases·Fangfeng YuanLeyi Wang
Dec 10, 2020·Nature Biomedical Engineering·Shibo JiangLanying Du
Dec 16, 2020·SLAS Discovery·Dawid MaciorowskiAdinarayana Kunamneni
Dec 31, 2020·Pharmacology Research & Perspectives·Camilla Servidio, Francesco Stellacci
Jan 1, 2021·PloS One·Nathan PostSharif A Ismail
Jan 5, 2021·Frontiers in Immunology·Yannick GalipeauMarc-André Langlois
Dec 29, 2020·Science Immunology·Catherine J ReynoldsRosemary J Boyton
Jan 14, 2021·Journal of Biomedical Science·Ioannis P TrougakosMeletios A Dimopoulos
Oct 25, 2020·The Protein Journal·Mihaela Ileana Ionescu

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Methods Mentioned

BETA
blood
ELISA
Flow cytometry
fluorescence activating cell sorting
enzyme-linked immunosorbent assay
PCR
biolayer interferometry
size exclusion chromatography
glycosylation

Software Mentioned

Graphpad
Data Analysis Software
MEGA7

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