ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
12 08 2022
12 08 2022
Historique:
pubmed:
21
7
2022
medline:
16
8
2022
entrez:
20
7
2022
Statut:
ppublish
Résumé
The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and betacoronaviruses, including animal coronaviruses WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses showed that the fusion peptide-specific mAbs bound with different modalities to a cryptic epitope hidden in prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs.
Identifiants
pubmed: 35857703
doi: 10.1126/science.abq2679
pmc: PMC9348755
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Viral
0
Broadly Neutralizing Antibodies
0
Peptides
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
735-742Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM133894
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM138396
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132317
Pays : United States
Références
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14
pubmed: 23793146
Nature. 1992 Jun 4;357(6377):420-2
pubmed: 1350662
Nature. 2021 Oct;598(7880):342-347
pubmed: 34464958
Nat Commun. 2022 Feb 15;13(1):719
pubmed: 35169114
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7348-E7357
pubmed: 28807998
Nat Struct Mol Biol. 2019 Oct;26(10):980-987
pubmed: 31570878
J Virol. 2004 Sep;78(17):9007-15
pubmed: 15308697
Science. 2022 Jan 28;375(6579):449-454
pubmed: 34990214
Science. 2020 Dec 11;370(6522):1339-1343
pubmed: 33159009
Mol Cell. 2022 Jun 2;82(11):2050-2068.e6
pubmed: 35447081
Nature. 2021 Feb;590(7845):320-325
pubmed: 33260195
Nat Med. 2021 Jan;27(1):106-114
pubmed: 33288923
J Virol. 2015 Jul;89(14):7202-13
pubmed: 25926653
Nature. 2020 Jul;583(7815):290-295
pubmed: 32422645
Mol Cell. 2020 May 21;78(4):779-784.e5
pubmed: 32362314
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22664-22672
pubmed: 31636219
Nat Med. 2018 May;24(4):401-407
pubmed: 29554084
Science. 2012 Sep 14;337(6100):1343-8
pubmed: 22878502
Sci Transl Med. 2022 Mar 23;14(637):eabi9215
pubmed: 35133175
Nature. 2021 Mar;591(7849):293-299
pubmed: 33494095
J Virol. 1993 Mar;67(3):1185-94
pubmed: 7679743
Nature. 2012 Nov 15;491(7424):406-12
pubmed: 23151583
Cell. 2020 Apr 16;181(2):281-292.e6
pubmed: 32155444
Nat Rev Immunol. 2019 Feb;19(2):77-78
pubmed: 30560910
Nature. 2003 Nov 27;426(6965):450-4
pubmed: 14647384
Immunol Rev. 2017 Jan;275(1):145-160
pubmed: 28133802
Nature. 2013 Nov 28;503(7477):535-8
pubmed: 24172901
Science. 2020 Aug 7;369(6504):731-736
pubmed: 32540900
Science. 2020 Sep 18;369(6510):1501-1505
pubmed: 32703906
Proc Natl Acad Sci U S A. 2005 May 31;102(22):7988-93
pubmed: 15897467
Nature. 2021 Sep;597(7874):97-102
pubmed: 34261126
Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5871-6
pubmed: 19321428
Nature. 2021 Sep;597(7874):103-108
pubmed: 34280951
Science. 2020 Nov 27;370(6520):
pubmed: 32994364
J Virol. 2004 Jul;78(13):6938-45
pubmed: 15194770
Nature. 2013 Mar 14;495(7440):251-4
pubmed: 23486063
Elife. 2021 Feb 08;10:
pubmed: 33554856
J Virol. 2009 Aug;83(15):7411-21
pubmed: 19439480
Cell. 2018 Jun 14;173(7):1783-1795.e14
pubmed: 29731169
Nature. 2022 Dec;612(7941):748-757
pubmed: 36477529
Proc Natl Acad Sci U S A. 2018 May 29;115(22):E5135-E5143
pubmed: 29760102
Nat Commun. 2021 Mar 17;12(1):1715
pubmed: 33731724
PLoS One. 2019 Apr 17;14(4):e0215163
pubmed: 30995238
Cell. 2022 Mar 3;185(5):872-880.e3
pubmed: 35123650
Cell Rep. 2021 Sep 28;36(13):109760
pubmed: 34534459
Sci Transl Med. 2022 Jan 26;14(629):eabj7125
pubmed: 34726473
Science. 2016 May 13;352(6287):828-33
pubmed: 27174988
Science. 2021 Sep 03;373(6559):1109-1116
pubmed: 34344823
Proc Natl Acad Sci U S A. 1988 Jun;85(12):4526-9
pubmed: 3380803
Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11157-11162
pubmed: 29073020
Sci Rep. 2020 Feb 20;10(1):3032
pubmed: 32080235
Nature. 2016 Mar 3;531(7592):114-117
pubmed: 26855426
J Immunol Methods. 2008 Jan 1;329(1-2):112-24
pubmed: 17996249
J Gen Virol. 2006 May;87(Pt 5):1209-1216
pubmed: 16603523
Science. 2011 Aug 12;333(6044):850-6
pubmed: 21798894
Science. 2011 Sep 16;333(6049):1633-7
pubmed: 21764753
Science. 2020 Nov 20;370(6519):950-957
pubmed: 32972994
Blood. 2013 May 16;121(20):4110-4
pubmed: 23550036
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Cell. 2022 Jun 23;185(13):2279-2291.e17
pubmed: 35700730
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2210-21
pubmed: 15572774
Nat Struct Mol Biol. 2021 Jun;28(6):478-486
pubmed: 33981021
Cell Host Microbe. 2021 Jan 13;29(1):44-57.e9
pubmed: 33259788
Annu Rev Immunol. 2013;31:705-42
pubmed: 23330954
Nat Med. 2015 Sep;21(9):1065-70
pubmed: 26301691
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
Cell Rep. 2022 May 3;39(5):110786
pubmed: 35477024
Antiviral Res. 1990 Oct-Nov;14(4-5):181-205
pubmed: 2088205
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):271-81
pubmed: 21460445
Nat Commun. 2020 Nov 17;11(1):5838
pubmed: 33203860
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Proc Natl Acad Sci U S A. 2022 Jan 4;119(1):
pubmed: 34930824
Nucleic Acids Res. 2013 Jul;41(Web Server issue):W34-40
pubmed: 23671333
Eur J Immunol. 2009 May;39(5):1260-70
pubmed: 19404981
EBioMedicine. 2021 Jun;68:103403
pubmed: 34049240
Science. 2015 Sep 18;349(6254):1301-6
pubmed: 26303961
Clin Infect Dis. 2022 Feb 11;74(3):446-454
pubmed: 34013321
Nature. 2021 Dec;600(7887):133-137
pubmed: 34789872
Cell. 2021 Apr 1;184(7):1858-1864.e10
pubmed: 33631096
J Struct Biol. 2005 Jul;151(1):41-60
pubmed: 15890530
J Virol. 2010 Apr;84(7):3210-9
pubmed: 20071581
Science. 2021 Jun 18;372(6548):1336-1341
pubmed: 34006597
Proc Natl Acad Sci U S A. 2020 Oct 27;117(43):26955-26965
pubmed: 33037151
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Cell. 2020 Nov 12;183(4):1024-1042.e21
pubmed: 32991844
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
J Virol Methods. 2009 Jun;158(1-2):171-9
pubmed: 19428587
Nat Commun. 2020 Jun 1;11(1):2806
pubmed: 32483236
Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15214-9
pubmed: 25288733
Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):12262-12267
pubmed: 27791014
Nat Med. 2018 Jun;24(6):857-867
pubmed: 29867235
Avian Dis. 2007 Mar;51(1):45-51
pubmed: 17461266
Viruses. 2020 May 06;12(5):
pubmed: 32384820
Protein Sci. 2018 Jan;27(1):14-25
pubmed: 28710774
Nat Commun. 2021 May 19;12(1):2938
pubmed: 34011939
Nature. 2013 Apr 25;496(7446):469-76
pubmed: 23552890
Cell. 2019 Feb 21;176(5):1026-1039.e15
pubmed: 30712865
Nat Immunol. 2018 Nov;19(11):1179-1188
pubmed: 30333615