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. 2020 Mar 13;367(6483):1260-1263.
doi: 10.1126/science.abb2507. Epub 2020 Feb 19.

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

Daniel Wrapp #  1 , Nianshuang Wang #  1 , Kizzmekia S Corbett  2 , Jory A Goldsmith  1 , Ching-Lin Hsieh  1 , Olubukola Abiona  2 , Barney S Graham  2 , Jason S McLellan  3
Affiliations

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

Daniel Wrapp et al. Science. .

Abstract

The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

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Figures

Fig. 1
Fig. 1. Structure of 2019-nCoV S in the prefusion conformation.
(A) Schematic of 2019-nCoV S primary structure colored by domain. Domains that were excluded from the ectodomain expression construct or could not be visualized in the final map are colored white. SS, signal sequence; S2′, S2′ protease cleavage site; FP, fusion peptide; HR1, heptad repeat 1; CH, central helix; CD, connector domain; HR2, heptad repeat 2; TM, transmembrane domain; CT, cytoplasmic tail. Arrows denote protease cleavage sites. (B) Side and top views of the prefusion structure of the 2019-nCoV S protein with a single RBD in the up conformation. The two RBD down protomers are shown as cryo-EM density in either white or gray and the RBD up protomer is shown in ribbons colored corresponding to the schematic in (A).
Fig. 2
Fig. 2. Structural comparison between 2019-nCoV S and SARS-CoV S.
(A) Single protomer of 2019-nCoV S with the RBD in the down conformation (left) is shown in ribbons colored according to Fig. 1. A protomer of 2019-nCoV S in the RBD up conformation is shown (center) next to a protomer of SARS-CoV S in the RBD up conformation (right), displayed as ribbons and colored white (PDB ID: 6CRZ). (B) RBDs of 2019-nCoV and SARS-CoV aligned based on the position of the adjacent NTD from the neighboring protomer. The 2019-nCoV RBD is colored green and the SARS-CoV RBD is colored white. The 2019-nCoV NTD is colored blue. (C) Structural domains from 2019-nCoV S have been aligned to their counterparts from SARS-CoV S as follows: NTD (top left), RBD (top right), SD1 and SD2 (bottom left), and S2 (bottom right).
Fig. 3
Fig. 3. 2019-nCoV S binds human ACE2 with high affinity.
(A) Surface plasmon resonance sensorgram showing the binding kinetics for human ACE2 and immobilized 2019-nCoV S. Data are shown as black lines, and the best fit of the data to a 1:1 binding model is shown in red. (B) Negative-stain EM 2D class averages of 2019-nCoV S bound by ACE2. Averages have been rotated so that ACE2 is positioned above the 2019-nCoV S protein with respect to the viral membrane. A diagram depicting the ACE2-bound 2019-nCoV S protein is shown (right) with ACE2 in blue and S protein protomers colored tan, pink, and green.
Fig. 4
Fig. 4. Antigenicity of the 2019-nCoV RBD.
(A) SARS-CoV RBD shown as a white molecular surface (PDB ID: 2AJF), with residues that vary in the 2019-nCoV RBD colored red. The ACE2-binding site is outlined with a black dashed line. (B) Biolayer interferometry sensorgram showing binding to ACE2 by the 2019-nCoV RBD-SD1. Binding data are shown as a black line, and the best fit of the data to a 1:1 binding model is shown in red. (C) Biolayer interferometry to measure cross-reactivity of the SARS-CoV RBD-directed antibodies S230, m396, and 80R. Sensor tips with immobilized antibodies were dipped into wells containing 2019-nCoV RBD-SD1, and the resulting data are shown as a black line.
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References

    1. Chan J. F., Yuan S., Kok K.-H., To K. K.-W., Chu H., Yang J., Xing F., Liu J., Yip C. C.-Y., Poon R. W.-S., Tsoi H.-W., Lo S. K.-F., Chan K.-H., Poon V. K.-M., Chan W.-M., Ip J. D., Cai J.-P., Cheng V. C.-C., Chen H., Hui C. K.-M., Yuen K.-Y., A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster. Lancet 395, 514–523 (2020). 10.1016/S0140-6736(20)30154-9 - DOI - PMC - PubMed
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wei Y., Wu W., Xie X., Yin W., Li H., Liu M., Xiao Y., Gao H., Guo L., Xie J., Wang G., Jiang R., Gao Z., Jin Q., Wang J., Cao B., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020). 10.1016/S0140-6736(20)30183-5 - DOI - PMC - PubMed
    1. Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., Song H., Huang B., Zhu N., Bi Y., Ma X., Zhan F., Wang L., Hu T., Zhou H., Hu Z., Zhou W., Zhao L., Chen J., Meng Y., Wang J., Lin Y., Yuan J., Xie Z., Ma J., Liu W. J., Wang D., Xu W., Holmes E. C., Gao G. F., Wu G., Chen W., Shi W., Tan W., Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet S0140-6736(20)30251-8 (2020). 10.1016/S0140-6736(20)30251-8 - DOI - PMC - PubMed
    1. Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W., Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y., Wang Q.-M., Zheng J.-J., Xu L., Holmes E. C., Zhang Y.-Z., A new coronavirus associated with human respiratory disease in China. Nature (2020). 10.1038/s41586-020-2008-3 - DOI - PMC - PubMed
    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., Xia J., Yu T., Zhang X., Zhang L., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 395, 507–513 (2020). 10.1016/S0140-6736(20)30211-7 - DOI - PMC - PubMed

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