| Property | Value |
|---|
|
?:abstract
|
-
The trimeric spike (S) protein of SARS-CoV-2 is the primary focus of most vaccine design and development efforts. Due to intrinsic instability typical of class I fusion proteins, S tends to prematurely refold to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yields. To support ongoing vaccine development efforts, we report the structure-based design of soluble S trimers with increased yields and stabilities, based on introduction of single point mutations and disulfide-bridges. We identify regions critical for stability: the heptad repeat region 1, the SD1 domain and position 614 in SD2. We combine a minimal selection of mostly interprotomeric mutations to create a stable S-closed variant with a 6.4-fold higher expression than the parental construct while no longer containing a heterologous trimerization domain. The cryo-EM structure reveals a correctly folded, predominantly closed pre-fusion conformation. Highly stable and well producing S protein and the increased understanding of S protein structure will support vaccine development and serological diagnostics.
|
|
?:creator
|
|
|
?:doi
|
|
|
?:doi
|
-
10.1038/s41467-020-20321-x
|
|
?:journal
|
|
|
?:license
|
|
|
?:pdf_json_files
|
-
document_parses/pdf_json/38f6d0380b46ca56aedb1e2fa4f6d07493f24979.json
|
|
?:pmc_json_files
|
-
document_parses/pmc_json/PMC7801441.xml.json
|
|
?:pmcid
|
|
|
?:pmid
|
|
|
?:pmid
|
|
|
?:publication_isRelatedTo_Disease
|
|
|
?:sha_id
|
|
|
?:source
|
|
|
?:title
|
-
Stabilizing the closed SARS-CoV-2 spike trimer
|
|
?:type
|
|
|
?:year
|
|
![[This page as RDF]](https://research.tib.eu/covid-19/static/rdf-icon.gif){kind=icon}