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

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

doi:10.1126/science.abd0826

articleScienceJul 23, 2020HYBRID OA

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

CHChing‐Lin Hsieh JAJory A. Goldsmith JMJeffrey M. Schaub AMAndrea M. DiVenere HKHung‐Che Kuo

The University of Texas at Austin

PubMed

Indexed incrossrefpubmed

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…

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Topics & keywords

Topics

Keywords

Ectodomain
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Vero cell
Spike (software development)
Severe acute respiratory syndrome coronavirus
Coronavirus disease 2019 (COVID-19)
Protein structure
Biophysics

UN Sustainable Development Goals

Good health and well-being

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