Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260‐1263. doi:10.1126/science.abb2507

Review written by:

Nicole A. Perry-Hauser, PhD, edited by Andreacarola Urso and Andrew Ressler

Green – a thorough protein structural analysis of SARS-CoV-2 S protein, helpful to design antigens to develop new vaccines and antibodies against the virus

Background: 2019-nCoV enters host cells using a trimer of densely glycosylated spike (S) proteins. Binding of the 2019-nCoV S protein to angiotensin-converting enzyme 2 (ACE2) results in destabilization of the prefusion trimer and large structural rearrangement of the S protein. More specifically, the receptor-binding domain (RBD) of S1 samples two conformations: 1) the “down” conformation which corresponds to a receptor-inaccessible state and 2) the “up” conformation that corresponds to a receptor-accessible state.


Results: Investigators structurally characterized the 2019-nCoV spike protein to 3.5 Å. Overall, the structure was similar to  SARS-CoV S except for the down RBDs conformation, where RBD domain of 2019-nCoV packed closer to the middle cavity of the trimer. Kinetic experiments revealed that the 2019-nCoV spike protein bound ACE2 with ~15 nM affinity, which is 10- to 20-fold higher than ACE2 interaction with SARS-CoV S. Three SARS-CoV RBD-directed monoclonal antibodies were tested for cross-reactivity to 2019-nCoV S without success.


Primary Methods: A) Cryo-electron microscopy to obtain structural data of the 2019 nCoV spike protein. B) Surface plasmon resonance and biolayer interferometry to measure kinetics of ACE2 and antibody binding to spike proteins.

Review Notes
 

Resolution is reasonable, but 3.5 Å still leaves room for improvement in structural analysis.

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