Structure-based evidence for the enhanced transmissibility of the dominant SARS-CoV-2 B.1.1.7 variant (Alpha)

doi:10.1038/s41421-021-00349-z

. 2021 Nov 9;7(1):109.

doi: 10.1038/s41421-021-00349-z.

Structure-based evidence for the enhanced transmissibility of the dominant SARS-CoV-2 B.1.1.7 variant (Alpha)

Shuai Xia^#¹, Zuoling Wen^#^{2

3}, Lijue Wang^#¹, Qiaoshuai Lan¹, Fanke Jiao¹, Linhua Tai^{2

3}, Qian Wang¹, Fei Sun^{2

3

4}, Shibo Jiang⁵, Lu Lu⁶, Yun Zhu⁷

Affiliations

¹ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
² National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
³ University of Chinese Academy of Sciences, Beijing, China.
⁴ Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong, China.
⁵ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China. shibojiang@fudan.edu.cn.
⁶ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China. lul@fudan.edu.cn.
⁷ National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. zhuyun@ibp.ac.cn.

^# Contributed equally.

PMID: 34750362
PMCID: PMC8576028
DOI: 10.1038/s41421-021-00349-z

Structure-based evidence for the enhanced transmissibility of the dominant SARS-CoV-2 B.1.1.7 variant (Alpha)

Shuai Xia et al. Cell Discov. 2021.

. 2021 Nov 9;7(1):109.

doi: 10.1038/s41421-021-00349-z.

Authors

Shuai Xia^#¹, Zuoling Wen^#^{2

3}, Lijue Wang^#¹, Qiaoshuai Lan¹, Fanke Jiao¹, Linhua Tai^{2

3}, Qian Wang¹, Fei Sun^{2

3

4}, Shibo Jiang⁵, Lu Lu⁶, Yun Zhu⁷

Affiliations

¹ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
² National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
³ University of Chinese Academy of Sciences, Beijing, China.
⁴ Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong, China.
⁵ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China. shibojiang@fudan.edu.cn.
⁶ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China. lul@fudan.edu.cn.
⁷ National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. zhuyun@ibp.ac.cn.

^# Contributed equally.

PMID: 34750362
PMCID: PMC8576028
DOI: 10.1038/s41421-021-00349-z

No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1. Structural and functional effects of mutations in the S protein of the SARS-CoV-2 B.1.1.7 (Alpha) variant on human lung cells.**
a Schematic representation of the B.1.1.7 SARS-CoV-2 S protein with ten natural mutations. The S1 subunit contains mainly an N-terminal domain (NTD), a receptor-binding domain (RBD), and subdomains 1 and 2 (SD1 and SD2). The S2 subunit contains a fusion peptide (FP), fusion peptide proximal region (FPPR), heptad repeats 1 and 2 (HR1 and HR2), a central helix (CH), a connector domain (CD), a transmembrane domain (TM) and a cytoplasmic tail (CT). b Overall structure of SARS-CoV-2 B.1.1.7 S in the 1-RBD-up state, indicating the natural mutations. c Overall structure of the SARS-CoV-2 B.1.1.7 S-ACE2 complex. The interface between the RBD and ACE2 is magnified to compare the structures of WT S-ACE2 (gray) and N501Y S-ACE2 (light blue). d The N501Y mutation site in the three structures mentioned in (c). e The A570D, D614G, P681H, T716I, S982A and D1118H mutation sites in the three structures mentioned in (c). f Structural model of furin with the cleavage sites in the SARS-CoV-2 and B.1.1.7 variants. g Representative images of cell–cell fusion between 293T/SARS-CoV-2(WT)/EGFP, 293T/SARS-CoV-2(D614G)/EGFP, 293T/SARS-CoV-2(B.1.1.7)/EGFP effector cells and target cells (Calu-3) after coculture for 6 h. Scale bars, 400 µm. h Western blot analysis of S protein expression in effector cells. i–m Statistical analysis of fusion rates mediated by the WT, D614G, and B.1.1.7 S protein after coculture for 1 h (i), 2 h (j), 3 h (k), 4 h (l), and 12 h (m). Asterisks indicate significant differences. *P < 0.05, **P < 0.01, ***P < 0.001. NS, not significant.

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References

1. Hoffmann M, et al. SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell. 2021;184:2384–2393. doi: 10.1016/j.cell.2021.03.036. - DOI - PMC - PubMed
1. Washington NL, et al. Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States. Cell. 2021;184:2587–2594.e7. doi: 10.1016/j.cell.2021.03.052. - DOI - PMC - PubMed
1. Zhu X, et al. Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies. PLoS Biol. 2021;19:e3001237. doi: 10.1371/journal.pbio.3001237. - DOI - PMC - PubMed
1. Socher E, et al. Mutations in the B.1.1.7 SARS-CoV-2 spike protein reduce receptor-binding affinity and induce a flexible link to the fusion peptide. Biomedicines. 2021;9:525. doi: 10.3390/biomedicines9050525. - DOI - PMC - PubMed
1. Niu Z, et al. N501Y mutation imparts cross-species transmission of SARS-CoV-2 to mice by enhancing receptor binding. Signal Transduct. Target. Ther. 2021;6:284. doi: 10.1038/s41392-021-00704-2. - DOI - PMC - PubMed

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[1] Hoffmann M, et al. SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell. 2021;184:2384–2393. doi: 10.1016/j.cell.2021.03.036. - DOI - PMC - PubMed

[2] Hoffmann M, et al. SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell. 2021;184:2384–2393. doi: 10.1016/j.cell.2021.03.036. - DOI - PMC - PubMed

[3] Washington NL, et al. Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States. Cell. 2021;184:2587–2594.e7. doi: 10.1016/j.cell.2021.03.052. - DOI - PMC - PubMed

[4] Washington NL, et al. Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States. Cell. 2021;184:2587–2594.e7. doi: 10.1016/j.cell.2021.03.052. - DOI - PMC - PubMed

[5] Zhu X, et al. Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies. PLoS Biol. 2021;19:e3001237. doi: 10.1371/journal.pbio.3001237. - DOI - PMC - PubMed

[6] Zhu X, et al. Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies. PLoS Biol. 2021;19:e3001237. doi: 10.1371/journal.pbio.3001237. - DOI - PMC - PubMed

[7] Socher E, et al. Mutations in the B.1.1.7 SARS-CoV-2 spike protein reduce receptor-binding affinity and induce a flexible link to the fusion peptide. Biomedicines. 2021;9:525. doi: 10.3390/biomedicines9050525. - DOI - PMC - PubMed

[8] Socher E, et al. Mutations in the B.1.1.7 SARS-CoV-2 spike protein reduce receptor-binding affinity and induce a flexible link to the fusion peptide. Biomedicines. 2021;9:525. doi: 10.3390/biomedicines9050525. - DOI - PMC - PubMed

[9] Niu Z, et al. N501Y mutation imparts cross-species transmission of SARS-CoV-2 to mice by enhancing receptor binding. Signal Transduct. Target. Ther. 2021;6:284. doi: 10.1038/s41392-021-00704-2. - DOI - PMC - PubMed

[10] Niu Z, et al. N501Y mutation imparts cross-species transmission of SARS-CoV-2 to mice by enhancing receptor binding. Signal Transduct. Target. Ther. 2021;6:284. doi: 10.1038/s41392-021-00704-2. - DOI - PMC - PubMed

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Structure-based evidence for the enhanced transmissibility of the dominant SARS-CoV-2 B.1.1.7 variant (Alpha)

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Structure-based evidence for the enhanced transmissibility of the dominant SARS-CoV-2 B.1.1.7 variant (Alpha)

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