Structure-based design of prefusion-stabilized SARS-CoV-2 spikes
- PMID: 32703906
- PMCID: PMC7402631
- DOI: 10.1126/science.abd0826
Structure-based design of prefusion-stabilized SARS-CoV-2 spikes
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. We characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions resulted in the identification of HexaPro, a variant with six beneficial proline substitutions exhibiting higher expression than its parental construct (by a factor of 10) as well as the ability to withstand heat stress, storage at room temperature, and three freeze-thaw cycles. A cryo-electron microscopy structure of HexaPro at a resolution of 3.2 angstroms confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes.bioRxiv [Preprint]. 2020 May 30:2020.05.30.125484. doi: 10.1101/2020.05.30.125484. bioRxiv. 2020. Update in: Science. 2020 Sep 18;369(6510):1501-1505. doi: 10.1126/science.abd0826. PMID: 32577660 Free PMC article. Updated. Preprint.
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