Structural Basis and Mode of Action for Two Broadly Neutralizing Antibodies Against SARS-CoV-2 Emerging Variants of Concern.


Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
03 Aug 2021
Historique:
entrez: 10 8 2021
pubmed: 11 8 2021
medline: 11 8 2021
Statut: epublish

Résumé

Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here we elucidate the structural basis and mode of action for two potent SARS-CoV-2 Spike (S) neutralizing monoclonal antibodies CV3-1 and CV3-25 that remained effective against emerging variants of concern in vitro and in vivo. CV3-1 bound to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the "RBD-up" position and triggered potent shedding of the S1 subunit. In contrast, CV3-25 inhibited membrane fusion by binding to an epitope in the stem helix region of the S2 subunit that is highly conserved among β-coronaviruses. Thus, vaccine immunogen designs that incorporate the conserved regions in RBD and stem helix region are candidates to elicit pan-coronavirus protective immune responses.

Identifiants

pubmed: 34373853
doi: 10.1101/2021.08.02.454546
pmc: PMC8351775
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI163395
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI055403
Pays : United States

Commentaires et corrections

Type : UpdateIn

Références

Sci Adv. 2021 Jan 1;7(1):
pubmed: 33277323
Methods Enzymol. 1997;277:366-96
pubmed: 18488318
Cell Rep Med. 2020 Oct 20;1(7):100126
pubmed: 33015650
Nat Commun. 2020 Mar 27;11(1):1620
pubmed: 32221306
Science. 2020 Aug 7;369(6504):643-650
pubmed: 32540902
Viruses. 2020 Sep 29;12(10):
pubmed: 33003587
Nat Struct Mol Biol. 2021 Feb;28(2):202-209
pubmed: 33432247
Euro Surveill. 2021 Jun;26(24):
pubmed: 34142653
Nature. 2020 Dec;588(7838):498-502
pubmed: 32805734
Emerg Microbes Infect. 2020 Dec;9(1):382-385
pubmed: 32065055
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Elife. 2020 Oct 28;9:
pubmed: 33112236
Science. 2021 Feb 19;371(6531):850-854
pubmed: 33495308
Science. 2012 May 25;336(6084):1030-3
pubmed: 22628654
Clin Infect Dis. 2021 Jul 09;:
pubmed: 34244723
J Struct Biol. 2013 Nov;184(2):261-70
pubmed: 23999189
J Virol. 2020 Dec 11;:
pubmed: 33310888
Science. 2020 Dec 11;370(6522):1339-1343
pubmed: 33159009
Cell Host Microbe. 2020 Sep 9;28(3):486-496.e6
pubmed: 32738193
Lancet. 2021 Jan 9;397(10269):99-111
pubmed: 33306989
N Engl J Med. 2021 Jun 10;384(23):2187-2201
pubmed: 33882225
J Exp Med. 2020 Nov 2;217(11):
pubmed: 32692348
Lancet. 2020 Aug 15;396(10249):467-478
pubmed: 32702298
J Struct Biol. 2017 Feb;197(2):191-198
pubmed: 27313000
N Engl J Med. 2020 Feb 20;382(8):727-733
pubmed: 31978945
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Nat Commun. 2020 May 4;11(1):2251
pubmed: 32366817
Cell. 2021 Apr 29;184(9):2384-2393.e12
pubmed: 33794143
Science. 2021 Aug 6;373(6555):
pubmed: 34168071
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
J Struct Biol. 2017 Feb;197(2):102-113
pubmed: 27444392
Lancet Microbe. 2020 Aug;1(4):e151
pubmed: 33521716
Nature. 2020 Aug;584(7821):450-456
pubmed: 32698192
Cell. 2020 Apr 16;181(2):281-292.e6
pubmed: 32155444
Nature. 2003 Nov 27;426(6965):450-4
pubmed: 14647384
Nucleic Acids Res. 2016 Jul 8;44(W1):W474-8
pubmed: 27131379
Acta Crystallogr D Struct Biol. 2017 Jun 1;73(Pt 6):469-477
pubmed: 28580908
Virol Sin. 2018 Feb;33(1):104-107
pubmed: 29500691
Nature. 2013 Nov 28;503(7477):535-8
pubmed: 24172901
Cell Host Microbe. 2021 Mar 10;29(3):463-476.e6
pubmed: 33592168
Science. 2020 Oct 9;370(6513):203-208
pubmed: 32817270
Nat Methods. 2015 Oct;12(10):943-6
pubmed: 26280328
Science. 2020 Sep 18;369(6510):1501-1505
pubmed: 32703906
mBio. 2017 Apr 4;8(2):
pubmed: 28377531
Cell Host Microbe. 2021 Mar 10;29(3):477-488.e4
pubmed: 33535027
Nature. 2020 May;581(7807):221-224
pubmed: 32225175
Cell Host Microbe. 2020 Dec 9;28(6):880-891.e8
pubmed: 33242391
Nature. 2020 Aug;584(7819):115-119
pubmed: 32454513
Lancet. 2021 Feb 20;397(10275):671-681
pubmed: 33545094
Nat Med. 2021 May;27(5):917-924
pubmed: 33772244
Nat Commun. 2021 Mar 17;12(1):1715
pubmed: 33731724
Protein Sci. 2021 Jan;30(1):70-82
pubmed: 32881101
mBio. 2020 Oct 16;11(5):
pubmed: 33067385
Cell. 2020 Oct 29;183(3):730-738.e13
pubmed: 32979942
J Mol Biol. 2007 Sep 21;372(3):774-97
pubmed: 17681537
Nat Microbiol. 2020 Apr;5(4):562-569
pubmed: 32094589
Science. 2020 Sep 25;369(6511):1586-1592
pubmed: 32694201
N Engl J Med. 2021 Feb 4;384(5):403-416
pubmed: 33378609
Lancet Infect Dis. 2020 May;20(5):533-534
pubmed: 32087114
Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3048-53
pubmed: 26976607
Nature. 2021 Aug;596(7871):276-280
pubmed: 34237773
Cell. 2020 Sep 3;182(5):1295-1310.e20
pubmed: 32841599
Nat Struct Mol Biol. 2021 Jun;28(6):478-486
pubmed: 33981021
Cell Host Microbe. 2021 Jul 14;29(7):1162-1162.e1
pubmed: 34265246
Cell Host Microbe. 2020 Apr 8;27(4):671-680.e2
pubmed: 32183941
Cell Host Microbe. 2021 Jan 13;29(1):44-57.e9
pubmed: 33259788
J Struct Biol. 2005 Oct;152(1):36-51
pubmed: 16182563
Cell Host Microbe. 2021 Mar 10;29(3):322-324
pubmed: 33705702
Acta Crystallogr D Biol Crystallogr. 2006 Aug;62(Pt 8):859-66
pubmed: 16855301
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
J Struct Biol. 2015 Nov;192(2):188-95
pubmed: 26296328
Nat Med. 2015 Dec;21(12):1508-13
pubmed: 26552008
Nature. 2020 Dec;588(7839):682-687
pubmed: 33045718
Cell Rep. 2021 Jul 13;36(2):109353
pubmed: 34237283
Nat Struct Mol Biol. 2020 Aug;27(8):726-734
pubmed: 32601441
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
Cell. 2020 Aug 20;182(4):828-842.e16
pubmed: 32645326
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Acta Crystallogr D Biol Crystallogr. 2003 Jul;59(Pt 7):1145-53
pubmed: 12832757
J Virol. 2021 Mar 16;:
pubmed: 33727331
Nature. 2021 May;593(7858):266-269
pubmed: 33767447
Nature. 2020 May;581(7807):215-220
pubmed: 32225176
N Engl J Med. 2020 Dec 31;383(27):2603-2615
pubmed: 33301246
N Engl J Med. 2021 May 13;384(19):1824-1835
pubmed: 33440088
Protein Sci. 2018 Jan;27(1):14-25
pubmed: 28710774
Nat Commun. 2021 May 19;12(1):2938
pubmed: 34011939
Cell. 2021 Apr 29;184(9):2332-2347.e16
pubmed: 33761326
J Struct Biol. 2007 Jan;157(1):126-37
pubmed: 16973379
Cell Host Microbe. 2021 Jul 14;29(7):1137-1150.e6
pubmed: 34133950
Curr Opin HIV AIDS. 2020 Sep;15(5):300-308
pubmed: 32769632

Auteurs

Wenwei Li (W)

Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.

Yaozong Chen (Y)

Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.

Jérémie Prévost (J)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.

Irfan Ullah (I)

Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520.

Maolin Lu (M)

Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.

Shang Yu Gong (SY)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.

Alexandra Tauzin (A)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.

Romain Gasser (R)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.

Dani Vézina (D)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.

Sai Priya Anand (SP)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.

Guillaume Goyette (G)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.

Debashree Chaterjee (D)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.

Shilei Ding (S)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.

William D Tolbert (WD)

Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.

Michael W Grunst (MW)

Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.

Yuxia Bo (Y)

Department of Biochemistry, Microbiology and Immunology, and Center for Infection, Immunity, and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada.

Shijian Zhang (S)

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.

Jonathan Richard (J)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.

Fei Zhou (F)

Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Rick K Huang (RK)

Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Lothar Esser (L)

Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Allison Zeher (A)

Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Marceline Côté (M)

Department of Biochemistry, Microbiology and Immunology, and Center for Infection, Immunity, and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada.

Priti Kumar (P)

Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520.

Joseph Sodroski (J)

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.

Di Xia (D)

Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Pradeep D Uchil (PD)

Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.

Marzena Pazgier (M)

Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.

Andrés Finzi (A)

Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.

Walther Mothes (W)

Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.

Classifications MeSH