Structure-guided covalent stabilization of coronavirus spike glycoprotein trimers in the closed conformation.
Nat Struct Mol Biol
; 27(10): 942-949, 2020 10.
Article
in English
| MEDLINE | ID: covidwho-700293
ABSTRACT
SARS-CoV-2 is the causative agent of the COVID-19 pandemic, with 10 million infections and more than 500,000 fatalities by June 2020. To initiate infection, the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface and fusion of the viral and host membranes. Prefusion SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design. However, its limited stability and conformational dynamics are limiting factors for developing countermeasures against this virus. We report here the design of a construct corresponding to the prefusion SARS-CoV-2 S ectodomain trimer, covalently stabilized by a disulfide bond in the closed conformation. Structural and antigenicity analyses show we successfully shut S in the closed state without otherwise altering its architecture. We demonstrate that this strategy is applicable to other ß-coronaviruses, such as SARS-CoV and MERS-CoV, and might become an important tool for structural biology, serology, vaccine design and immunology studies.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Spike Glycoprotein, Coronavirus
/
Betacoronavirus
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Nat Struct Mol Biol
Journal subject:
Molecular Biology
Year:
2020
Document Type:
Article
Affiliation country:
S41594-020-0483-8
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