Cold sensitivity of the SARS-CoV-2 spike ectodomain

  1. Robert J Edwards
  2. Katayoun Mansouri
  3. Victoria Stalls
  4. Kartik Manne
  5. Brian Watts
  6. Rob Parks
  7. Katarzyna Janowska
  8. Sophie M. C. Gobeil
  9. Megan Kopp
  10. Dapeng Li
  11. Xiaozhi Lu
  12. Zekun Mu
  13. Margaret Deyton
  14. Thomas H Oguin
  15. Jordan Sprenz
  16. Wilton Williams
  17. Kevin Saunders
  18. David Montefiori
  19. Gregory D. Sempowski
  20. Rory Henderson
  21. Munir Alam
  22. Barton F. Haynes
  23. Priyamvada Acharya
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Abstract

The SARS-CoV-2 spike (S) protein, a primary target for COVID-19 vaccine development, presents its Receptor Binding Domain in two conformations: receptor-accessible “up” or receptor-inaccessible “down” conformations. Here, we report that the commonly used stabilized S ectodomain construct “2P” is sensitive to cold temperature, and that this cold sensitivity is resolved in a “down” state stabilized spike. Our results will impact structural, functional and vaccine studies that use the SARS-CoV-2 S ectodomain.

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