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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 C; 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.
Affiliation
  • Hsieh CL; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Goldsmith JA; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Schaub JM; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • DiVenere AM; Department of Chemical Engineering, University of Texas, Austin, TX 78712, USA.
  • Kuo HC; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Javanmardi K; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Le KC; Department of Chemical Engineering, University of Texas, Austin, TX 78712, USA.
  • Wrapp D; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Lee AG; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Liu Y; Department of Chemical Engineering, University of Texas, Austin, TX 78712, USA.
  • Chou CW; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Byrne PO; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Hjorth CK; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Johnson NV; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Ludes-Meyers J; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Nguyen AW; Department of Chemical Engineering, University of Texas, Austin, TX 78712, USA.
  • Park J; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Wang N; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Amengor D; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Lavinder JJ; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Ippolito GC; Department of Chemical Engineering, University of Texas, Austin, TX 78712, USA.
  • Maynard JA; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Finkelstein IJ; Department of Oncology, Dell Medical School, University of Texas, Austin, TX 78712, USA.
  • McLellan JS; Department of Chemical Engineering, University of Texas, Austin, TX 78712, USA. maynard@che.utexas.edu ilya@finkelsteinlab.org jmclellan@austin.utexas.edu.
Science ; 369(6510): 1501-1505, 2020 09 18.
Article in En | MEDLINE | ID: mdl-32703906
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).
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Amino Acid Substitution / Spike Glycoprotein, Coronavirus / Betacoronavirus Type of study: Prognostic_studies Limits: Humans Language: En Journal: Science Year: 2020 Document type: Article Affiliation country: Estados Unidos
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Amino Acid Substitution / Spike Glycoprotein, Coronavirus / Betacoronavirus Type of study: Prognostic_studies Limits: Humans Language: En Journal: Science Year: 2020 Document type: Article Affiliation country: Estados Unidos