Highly synergistic combinations of nanobodies that target SARS-CoV-2 and are resistant to escape.
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Binding Sites
COVID-19
/ immunology
Camelids, New World
/ immunology
Epitopes
/ genetics
HEK293 Cells
Humans
Male
Neutralization Tests
SARS-CoV-2
/ genetics
Single-Domain Antibodies
/ immunology
Spike Glycoprotein, Coronavirus
/ genetics
SARS-CoV-2
human
infectious disease
microbiology
nanobodies
single-domain antibodies
spike glycoprotein
synergy
variants of concern
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
07 12 2021
07 12 2021
Historique:
received:
13
08
2021
accepted:
07
11
2021
entrez:
7
12
2021
pubmed:
8
12
2021
medline:
16
12
2021
Statut:
epublish
Résumé
The emergence of SARS-CoV-2 variants threatens current vaccines and therapeutic antibodies and urgently demands powerful new therapeutics that can resist viral escape. We therefore generated a large nanobody repertoire to saturate the distinct and highly conserved available epitope space of SARS-CoV-2 spike, including the S1 receptor binding domain, N-terminal domain, and the S2 subunit, to identify new nanobody binding sites that may reflect novel mechanisms of viral neutralization. Structural mapping and functional assays show that indeed these highly stable monovalent nanobodies potently inhibit SARS-CoV-2 infection, display numerous neutralization mechanisms, are effective against emerging variants of concern, and are resistant to mutational escape. Rational combinations of these nanobodies that bind to distinct sites within and between spike subunits exhibit extraordinary synergy and suggest multiple tailored therapeutic and prophylactic strategies.
Identifiants
pubmed: 34874007
doi: 10.7554/eLife.73027
pii: 73027
pmc: PMC8651292
doi:
pii:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Epitopes
0
Single-Domain Antibodies
0
Spike Glycoprotein, Coronavirus
0
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
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI078788
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM112108
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI125378
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM109824
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI150991
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2021, Mast et al.
Déclaration de conflit d'intérêts
FM, PF, NK, JW, EJ, JO, JA, BC, MR Inventor on a provisional patent describing the anti-spike nanobodies described in this manuscript, TS, KM, FS, MR, YW, LR, EV, ND, VV, SK, JJ, MS, PO, TH, DS, JD, DF, AS, PB No competing interests declared, LH Louis Herlands is affiliated with AbOde Therapeutics Inc. The author has no financial interests to declare
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