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

doi:10.1126/science.abd0826

GSTDTAP > 气候变化

DOI	10.1126/science.abd0826
	Structure-based design of prefusion-stabilized SARS-CoV-2 spikes
	Ching-Lin Hsieh; Jory A. Goldsmith; Jeffrey M. Schaub; Andrea M. DiVenere; Hung-Che Kuo; Kamyab Javanmardi; Kevin C. 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
	2020-09-18
发表期刊	Science
出版年	2020
英文摘要	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][1] 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). [1]: /lookup/doi/10.1126/science.abd0826
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/295431
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Ching-Lin Hsieh,Jory A. Goldsmith,Jeffrey M. Schaub,et al. Structure-based design of prefusion-stabilized SARS-CoV-2 spikes[J]. Science,2020.
APA	Ching-Lin Hsieh.,Jory A. Goldsmith.,Jeffrey M. Schaub.,Andrea M. DiVenere.,Hung-Che Kuo.,...&Jason S. McLellan.(2020).Structure-based design of prefusion-stabilized SARS-CoV-2 spikes.Science.
MLA	Ching-Lin Hsieh,et al."Structure-based design of prefusion-stabilized SARS-CoV-2 spikes".Science (2020).