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Stabilizing the closed SARS-CoV-2 spike trimer. | LitMetric

Stabilizing the closed SARS-CoV-2 spike trimer.

Nat Commun

Janssen Vaccines & Prevention B.V., Archimedesweg 4-6, Leiden, The Netherlands.

Published: January 2021

AI Article Synopsis

  • * Researchers have engineered improved versions of soluble S trimers by introducing specific mutations and disulfide bridges, enhancing their stability and yield.
  • * The newly designed stable S-closed variant shows a significantly higher expression rate and maintains a correct pre-fusion structure, which can aid in vaccine and diagnostic advancements.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801441PMC
http://dx.doi.org/10.1038/s41467-020-20321-xDOI Listing

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