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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
Science, 09/2020, Letnik: 369, Številka: 6510Journal Article
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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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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