Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms.
Amino Acid Motifs
/ immunology
Angiotensin-Converting Enzyme 2
Animals
Antibodies, Neutralizing
/ administration & dosage
Antibodies, Viral
/ administration & dosage
Betacoronavirus
/ immunology
CHO Cells
COVID-19
Coronavirus Infections
/ prevention & control
Cricetinae
Cricetulus
Cryoelectron Microscopy
HEK293 Cells
Humans
Immunodominant Epitopes
/ chemistry
Microscopy, Electron
Pandemics
/ prevention & control
Peptidyl-Dipeptidase A
/ immunology
Pneumonia, Viral
/ prevention & control
Protein Domains
/ immunology
SARS-CoV-2
Spike Glycoprotein, Coronavirus
/ antagonists & inhibitors
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
20 11 2020
20 11 2020
Historique:
received:
14
08
2020
accepted:
21
09
2020
pubmed:
26
9
2020
medline:
2
12
2020
entrez:
25
9
2020
Statut:
ppublish
Résumé
Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.
Identifiants
pubmed: 32972994
pii: science.abe3354
doi: 10.1126/science.abe3354
pmc: PMC7857395
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Immunodominant Epitopes
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Peptidyl-Dipeptidase A
EC 3.4.15.1
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
950-957Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201700059C
Pays : United States
Organisme : Bill & Melinda Gates Foundation
ID : INV-006366
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM120553
Pays : United States
Organisme : NIH HHS
ID : S10 OD023476
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Références
Nature. 2020 Aug;584(7819):120-124
pubmed: 32454512
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Microbiol Spectr. 2016 Dec;4(6):
pubmed: 28087938
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W503-8
pubmed: 18503082
Nature. 2020 May;581(7807):221-224
pubmed: 32225175
Nat Struct Mol Biol. 2020 Oct;27(10):942-949
pubmed: 32753755
Nature. 2020 Aug;584(7819):115-119
pubmed: 32454513
Nature. 2020 Aug;584(7821):443-449
pubmed: 32668443
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1591-1596
pubmed: 30642974
Cell. 2020 Sep 3;182(5):1284-1294.e9
pubmed: 32730807
J Struct Biol. 2005 Jul;151(1):41-60
pubmed: 15890530
Cell. 2020 May 14;181(4):894-904.e9
pubmed: 32275855
Science. 2020 Aug 21;369(6506):1010-1014
pubmed: 32540901
Nature. 2020 Dec;588(7838):498-502
pubmed: 32805734
Nature. 2020 Aug;584(7821):437-442
pubmed: 32555388
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
J Immunol. 2020 Aug 15;205(4):915-922
pubmed: 32591393
Elife. 2016 Nov 15;5:
pubmed: 27845625
Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7348-E7357
pubmed: 28807998
N Engl J Med. 2003 May 15;348(20):1953-66
pubmed: 12690092
Structure. 2019 Jan 2;27(1):134-139.e3
pubmed: 30344107
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67
pubmed: 21460454
Lancet. 2020 Aug 15;396(10249):467-478
pubmed: 32702298
Nature. 2020 Jul;583(7815):290-295
pubmed: 32422645
Nat Struct Mol Biol. 2015 Nov;22(11):833-4
pubmed: 26581513
N Engl J Med. 2020 Feb 20;382(8):727-733
pubmed: 31978945
N Engl J Med. 2020 Nov 12;383(20):1920-1931
pubmed: 32663912
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Elife. 2016 Sep 26;5:
pubmed: 27669148
Antiviral Res. 2016 Apr;128:7-19
pubmed: 26794397
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
Sci Rep. 2017 Dec 7;7(1):17169
pubmed: 29215033
Nature. 2020 Aug;584(7821):450-456
pubmed: 32698192
Cell. 2020 Apr 16;181(2):281-292.e6
pubmed: 32155444
mBio. 2018 Sep 11;9(5):
pubmed: 30206174
Science. 2020 Sep 18;369(6510):1501-1505
pubmed: 32703906
IUCrJ. 2019 Jan 01;6(Pt 1):5-17
pubmed: 30713699
Nat Methods. 2015 Apr;12(4):361-365
pubmed: 25707030
Nat Immunol. 2015 Feb;16(2):170-177
pubmed: 25501631
N Engl J Med. 2003 May 15;348(20):1967-76
pubmed: 12690091
Science. 2020 Aug 21;369(6506):956-963
pubmed: 32540903
Cell Host Microbe. 2020 Sep 9;28(3):475-485.e5
pubmed: 32735849
Nat Microbiol. 2020 Apr;5(4):562-569
pubmed: 32094589
Ultramicroscopy. 2013 Dec;135:24-35
pubmed: 23872039
Science. 2020 Jun 12;368(6496):1274-1278
pubmed: 32404477
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Adv Virus Res. 2019;105:93-116
pubmed: 31522710
Cell. 2020 Sep 3;182(5):1295-1310.e20
pubmed: 32841599
Immunity. 2018 Apr 17;48(4):799-811.e9
pubmed: 29669253
Lancet. 2020 Jun 13;395(10240):1845-1854
pubmed: 32450106
Nat Commun. 2020 Oct 15;11(1):5214
pubmed: 33060595
Antiviral Res. 1990 Oct-Nov;14(4-5):181-205
pubmed: 2088205
Elife. 2018 Nov 09;7:
pubmed: 30412051
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Science. 2020 Mar 27;367(6485):1444-1448
pubmed: 32132184
Science. 2020 Aug 14;369(6505):806-811
pubmed: 32434945
Nat Commun. 2020 Mar 27;11(1):1620
pubmed: 32221306
Nat Methods. 2020 Dec;17(12):1214-1221
pubmed: 33257830
PLoS Pathog. 2018 Feb 26;14(2):e1006934
pubmed: 29481552
Curr Biol. 2020 Jun 8;30(11):2196-2203.e3
pubmed: 32416074
Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18950-5
pubmed: 20956322
Science. 2020 Aug 7;369(6504):643-650
pubmed: 32540902
Cell. 2020 Aug 20;182(4):828-842.e16
pubmed: 32645326
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Cell. 2020 Nov 12;183(4):1024-1042.e21
pubmed: 32991844
Nat Methods. 2019 Nov;16(11):1146-1152
pubmed: 31591575
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
PLoS Pathog. 2015 May 29;11(5):e1004932
pubmed: 26023780
Nature. 2020 May;581(7807):215-220
pubmed: 32225176
Protein Sci. 2018 Jan;27(1):14-25
pubmed: 28710774
Cell. 2019 Feb 21;176(5):1026-1039.e15
pubmed: 30712865
Sci Rep. 2018 Oct 24;8(1):15701
pubmed: 30356097