scholarly journals Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes

Author(s):  
Ching-Lin Hsieh ◽  
Jory A. Goldsmith ◽  
Jeffrey M. Schaub ◽  
Andrea M. DiVenere ◽  
Hung-Che Kuo ◽  
...  

ABSTRACTThe COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to accelerated efforts to develop therapeutics, diagnostics, and vaccines to mitigate this public health emergency. A key target of these efforts is the spike (S) protein, a large trimeric class I fusion protein that is metastable and difficult to produce recombinantly in large quantities. Here, we designed and expressed over 100 structure-guided spike variants based upon a previously determined cryo-EM structure of the prefusion SARS-CoV-2 spike. Biochemical, biophysical and structural characterization of these variants identified numerous individual substitutions that increased protein yields and stability. The best variant, HexaPro, has six beneficial proline substitutions leading to ∼10-fold higher expression than its parental construct and is able to withstand heat stress, storage at room temperature, and multiple freeze-thaws. A 3.2 Å-resolution cryo-EM structure of HexaPro 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 SARS-CoV-2.

Science ◽  
2020 ◽  
Vol 369 (6510) ◽  
pp. 1501-1505 ◽  
Author(s):  
Ching-Lin Hsieh ◽  
Jory A. Goldsmith ◽  
Jeffrey M. Schaub ◽  
Andrea M. DiVenere ◽  
Hung-Che Kuo ◽  
...  

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).


2009 ◽  
Vol 66 (1) ◽  
pp. 22-27 ◽  
Author(s):  
Akihiro Meta ◽  
Hiroshi Nakatake ◽  
Takayuki Imamura ◽  
Chikateru Nozaki ◽  
Kazuhisa Sugimura

2015 ◽  
Vol 17 (5) ◽  
pp. 2769-2773 ◽  
Author(s):  
Ji Su ◽  
Mi Lu ◽  
Hongfei Lin

A new CO2 utilization strategy was developed via hydrogenation of CO2 derived ammonium carbamate/carbonate to produce value-added formate.


2020 ◽  
Author(s):  
Ying Yan

UNSTRUCTURED The ongoing outbreak of SARS-CoV-2 infection was first identified in Wuhan, China at the late of 2019. Following the acceleration of the novel coronavirus spreading, person-person transmissions in family residences, hospitals and other public environments have led to a major public hazard in China. Currently, the SARS-CoV-2 outbreak has been further developed into a public health emergency of international concern. In response to an occurring pandemic, hospitals need an emergency strategy and plan to manage their space, staff, and other essential resources, therefore, to provide optimum care to patients involved. In addition, infection prevention measures urgently need to be implemented to reduce in-hospital transmission and avoid the occurrence of virus super-spreading. For hospitals without capacity to manage severe patients, a referral network is often needed. We present our successful field experience regarding hospital emergency management and local hospitals network model in response to SARS-CoV-2 emerging epidemic.


animal ◽  
2021 ◽  
pp. 100293
Author(s):  
J. Simões ◽  
J.A. Abecia ◽  
A. Cannas ◽  
J.A. Delgadillo ◽  
D. Lacasta ◽  
...  

2021 ◽  
pp. 2101017
Author(s):  
Frank Mickoleit ◽  
Sabine Rosenfeldt ◽  
Mauricio Toro‐Nahuelpan ◽  
Miroslava Schaffer ◽  
Anna S. Schenk ◽  
...  

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