Structural basis for broad coronavirus neutralization.
Nat Struct Mol Biol
; 28(6): 478-486, 2021 06.
Article
in English
| MEDLINE | ID: covidwho-1226434
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
Three highly pathogenic ß-coronaviruses have crossed the animal-to-human species barrier in the past two decades SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight ß-coronavirus spike glycoproteins, including all five human-infecting ß-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with ß-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-ß-coronavirus vaccine.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Coronavirus Infections
/
Antibodies, Neutralizing
/
Spike Glycoprotein, Coronavirus
/
Betacoronavirus
/
Antibodies, Monoclonal
/
Antibodies, Viral
Type of study:
Experimental Studies
/
Randomized controlled trials
Topics:
Vaccines
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Nat Struct Mol Biol
Journal subject:
Molecular Biology
Year:
2021
Document Type:
Article
Affiliation country:
S41594-021-00596-4
Similar
MEDLINE
...
LILACS
LIS