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

  1. Yutong Song
  2. Hangping Yao
  3. Nanping Wu
  4. Jialu Xu
  5. Zheyuan Zhang
  6. Cheng Peng
  7. Shibo Li
  8. Weizheng Kong
  9. Yong Chen
  10. Miaojin Zhu
  11. Jiaqi Wang
  12. Danrong Shi
  13. Chongchong Zhao
  14. Xiangyun Lu
  15. Martín Echavarría Galindo
  16. Sai Li

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Abstract

Among the current five Variants of Concern, infections caused by 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, the architecture of intact Delta virions remains veiled. Moreover, pieces of molecular evidence for the detailed mechanism of S-mediated membrane fusion are missing. Here, we showed the pleomorphic nature of Delta virions from electron beam inactivated samples and reported the in situ structure and distribution of S on the authentic Delta variant. We also captured the virus–virus fusion events, which provided pieces of structural evidence for Delta’s attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Besides, site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S than that of the WT S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant.

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  1. Version published to 10.1073/pnas.2213332120
  2. Version published to 10.1101/2022.05.13.491759v2 on bioRxiv
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    SciScore for 10.1101/2022.05.13.491759: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  4. Version published to 10.1101/2022.05.13.491759v1 on bioRxiv