Rxivist logo

Closing coronavirus spike glycoproteins by structure-guided design

By Matthew McCallum, Alexandra C Walls, Davide Corti, David Veesler

Posted 03 Jun 2020
bioRxiv DOI: 10.1101/2020.06.03.129817

The recent spillover of SARS-CoV-2 in the human population resulted in the ongoing COVID-19 pandemic which has already caused 4.9 million infections and more than 326,000 fatalities. To initiate infection the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface, determining host and tissue tropism, and fusion of the viral and host membranes. Although SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design, its stability and conformational dynamics are limiting factors for developing countermeasures against this virus. We report here the design of a prefusion SARS-CoV-2 S ectodomain trimer construct covalently stabilized in the closed conformation. Structural and antigenicity analysis showed we successfully shut S in the closed state without otherwise altering its architecture. Finally, we show that this engineering strategy is applicable to other beta-coronavirus S glycoproteins and might become an important tool for vaccine design, structural biology, serology and immunology studies. ### Competing Interest Statement The authors have declared no competing interest.

Download data

  • Downloaded 1,269 times
  • Download rankings, all-time:
    • Site-wide: 16,767
    • In biochemistry: 343
  • Year to date:
    • Site-wide: 38,501
  • Since beginning of last month:
    • Site-wide: 26,458

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide