Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.
Angiotensin-Converting Enzyme 2
Antibodies, Monoclonal
/ immunology
Antibodies, Viral
/ immunology
Betacoronavirus
/ chemistry
Cross Reactions
Cryoelectron Microscopy
Image Processing, Computer-Assisted
Models, Molecular
Peptidyl-Dipeptidase A
/ metabolism
Protein Binding
Protein Conformation
Protein Domains
Protein Multimerization
Receptors, Coronavirus
Receptors, Virus
/ metabolism
Severe acute respiratory syndrome-related coronavirus
/ chemistry
SARS-CoV-2
Spike Glycoprotein, Coronavirus
/ chemistry
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
13 03 2020
13 03 2020
Historique:
received:
10
02
2020
accepted:
17
02
2020
pubmed:
23
2
2020
medline:
20
3
2020
entrez:
21
2
2020
Statut:
ppublish
Résumé
The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.
Identifiants
pubmed: 32075877
pii: science.abb2507
doi: 10.1126/science.abb2507
pmc: PMC7164637
mid: NIHMS1576935
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Viral
0
Receptors, Coronavirus
0
Receptors, Virus
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Peptidyl-Dipeptidase A
EC 3.4.15.1
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
1260-1263Subventions
Organisme : NIAID NIH HHS
ID : R01 AI127521
Pays : United States
Commentaires et corrections
Type : UpdateOf
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.
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