Structure-based design of prefusion-stabilized SARS-CoV-2 spikes

Ching‐Lin Hsieh , Jory A. Goldsmith , Jeffrey M. Schaub , Ching‐Lin Hsieh , Jory A. Goldsmith , Jeffrey M. Schaub , Andrea M. DiVenere , Hung-Che Kuo , Kamyab Javanmardi , Kevin Le , Daniel Wrapp , Alison G. Lee , Yutong Liu , Chia‐Wei Chou , Patrick O. Byrne , Christy K. Hjorth , Nicole V. Johnson , John Ludes-Meyers , Annalee W. Nguyen , Juyeon Park , Nianshuang Wang , Dzifa Amengor , Jason J. Lavinder , Gregory C. Ippolito , Jennifer A. Maynard , Ilya J. Finkelstein , Jason S. McLellan
2020 Science 1,349 citations

Abstract

Stabilizing the prefusion SARS-CoV-2 spike The development of therapeutic antibodies and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on the spike (S) protein that decorates the viral surface. A version of the spike ectodomain that includes two proline substitutions (S-2P) and stabilizes the prefusion conformation has been used to determine high-resolution structures. However, even S-2P is unstable and difficult to produce in mammalian cells. Hsieh et al. characterized many individual and combined structure-guided substitutions and identified a variant, named HexaPro, that retains the prefusion conformation but shows higher expression than S-2P and can also withstand heating and freezing. This version of the protein is likely to be useful in the development of vaccines and diagnostics. Science , this issue p. 1501

Keywords

EctodomainSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Vero cellSpike (software development)Severe acute respiratory syndrome coronavirusCoronavirus disease 2019 (COVID-19)Protein structureBiophysicsCoronavirusVirology2019-20 coronavirus outbreakComputational biologyBiologyChemistryVirusMedicineComputer scienceGeneticsBiochemistry

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Year
2020
Type
article
Volume
369
Issue
6510
Pages
1501-1505
Citations
1349
Access
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Ching‐Lin Hsieh, Jory A. Goldsmith, Jeffrey M. Schaub et al. (2020). Structure-based design of prefusion-stabilized SARS-CoV-2 spikes. Science , 369 (6510) , 1501-1505. https://doi.org/10.1126/science.abd0826

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DOI
10.1126/science.abd0826