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In situ architecture and membrane fusion of SARS-CoV-2 Delta variant

View ORCID ProfileYutong Song, View ORCID ProfileHangping Yao, Nanping Wu, View ORCID ProfileZheyuan Zhang, View ORCID ProfileJialu Xu, View ORCID ProfileCheng Peng, Shibo Li, View ORCID ProfileWeizheng Kong, View ORCID ProfileYong Chen, Miaojin Zhu, Jiaqi Wang, Danrong Shi, Chongchong Zhao, Xiangyun Lu, Martín Echavarría Galindo, View ORCID ProfileSai Li
doi: https://doi.org/10.1101/2022.05.13.491759
Yutong Song
1Beijing Frontier Research Center for Biological Structure & Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
2Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
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Hangping Yao
3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
4National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Nanping Wu
3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
4National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Zheyuan Zhang
1Beijing Frontier Research Center for Biological Structure & Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
2Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
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Jialu Xu
1Beijing Frontier Research Center for Biological Structure & Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
2Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
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Cheng Peng
1Beijing Frontier Research Center for Biological Structure & Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
2Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
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Shibo Li
5Department of Infectious Disease, Zhoushan Hospital, Zhejiang University, Zhoushan 316021, Zhejiang Province, China
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Weizheng Kong
1Beijing Frontier Research Center for Biological Structure & Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
2Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
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Yong Chen
1Beijing Frontier Research Center for Biological Structure & Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
2Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
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Miaojin Zhu
3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
4National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Jiaqi Wang
1Beijing Frontier Research Center for Biological Structure & Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
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Danrong Shi
3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
4National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Chongchong Zhao
1Beijing Frontier Research Center for Biological Structure & Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
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Xiangyun Lu
3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
4National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Martín Echavarría Galindo
1Beijing Frontier Research Center for Biological Structure & Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
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Sai Li
1Beijing Frontier Research Center for Biological Structure & Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
2Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
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  • For correspondence: sai@tsinghua.edu.cn
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SUMMARY

Among the current five Variants of Concern, infections caused by the SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, architecture of intact Delta virions remains veiled. Moreover, the detailed mechanism of S-mediated membrane fusion remains elusive. Here we report the molecular assembly and fusion snapshots of the authentic Delta variant. Envelope invagination and fusion events were frequently observed. Native structures of pre- and postfusion S were determined up to 4.1-Å resolution. Site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S over that of the Wuhan-Hu-1 S. Based on these findings, we proposed a model for S-mediated membrane fusion and a model for the invagination formation.

In Brief Cryo-ET of intact SARS-CoV-2 Delta variant revealed its unique architecture and captured snapshots of its membrane fusion in action.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 13, 2022.
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In situ architecture and membrane fusion of SARS-CoV-2 Delta variant
Yutong Song, Hangping Yao, Nanping Wu, Zheyuan Zhang, Jialu Xu, Cheng Peng, Shibo Li, Weizheng Kong, Yong Chen, Miaojin Zhu, Jiaqi Wang, Danrong Shi, Chongchong Zhao, Xiangyun Lu, Martín Echavarría Galindo, Sai Li
bioRxiv 2022.05.13.491759; doi: https://doi.org/10.1101/2022.05.13.491759
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In situ architecture and membrane fusion of SARS-CoV-2 Delta variant
Yutong Song, Hangping Yao, Nanping Wu, Zheyuan Zhang, Jialu Xu, Cheng Peng, Shibo Li, Weizheng Kong, Yong Chen, Miaojin Zhu, Jiaqi Wang, Danrong Shi, Chongchong Zhao, Xiangyun Lu, Martín Echavarría Galindo, Sai Li
bioRxiv 2022.05.13.491759; doi: https://doi.org/10.1101/2022.05.13.491759

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