Comprehensive analysis of the host-virus interactome of SARS-CoV-2

  1. Zhen Chen
  2. Chao Wang
  3. Xu Feng
  4. Litong Nie
  5. Mengfan Tang
  6. Huimin Zhang
  7. Yun Xiong
  8. Samuel K. Swisher
  9. Mrinal Srivastava
  10. Junjie Chen

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Abstract

Host-virus protein-protein interaction is the key component of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle. We conducted a comprehensive interactome study between the virus and host cells using tandem affinity purification and proximity labeling strategies and identified 437 human proteins as the high-confidence interacting proteins. Functional characterization and further validation of these interactions elucidated how distinct SARS-CoV-2 viral proteins participate in its lifecycle, and discovered potential drug targets to the treatment of COVID-19. The interactomes of two key SARS-CoV-2 encoded viral proteins, NSP1 and N protein, were compared with the interactomes of their counterparts in other human coronaviruses. These comparisons not only revealed common host pathways these viruses manipulate for their survival, but also showed divergent protein-protein interactions that may explain differences in disease pathology. This comprehensive interactome of coronavirus disease-2019 provides valuable resources for understanding and treating this disease.

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  1. ScreenIT

    SciScore for 10.1101/2020.12.31.424961: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    HEK293T and U2OS cell lines were purchased from American Type Culture Collection.
    HEK293T
    suggested: None
    U2OS cells were cultured on coverslips overnight and then transfected with construct encoding SARS-CoV-2 viral gene or vector control.
    U2OS
    suggested: CLS Cat# 300364/p489_U-2_OS, RRID:CVCL_0042)
    Software and Algorithms
    SentencesResources
    The raw MS data were submitted to Mascot 2.5 (Matrix Science) using Proteome Discoverer 2.2 (Thermo Fisher Scientific).
    Proteome Discoverer
    suggested: (Proteome Discoverer, RRID:SCR_014477)
    The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD023209. High-Confidence Interacting Proteins: The identified protein lists were applied to a filtration strategy by comparing with lists obtained from controls to uncover HCIPs.
    PRIDE
    suggested: (Pride-asap, RRID:SCR_012052)
    The host-virus interactome network was generated by Cytoscape and based on these HCIPs.
    Cytoscape
    suggested: (Cytoscape, RRID:SCR_003032)
    Functional characterization was carried out by Metascape65 or Ingenuity Pathway Analysis (Qiagen)
    Ingenuity Pathway Analysis
    suggested: (Ingenuity Pathway Analysis, RRID:SCR_008653)

    Results from OddPub: Thank you for sharing your data.

    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.

    About SciScore

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  2. Version published to 10.1101/2020.12.31.424961v1 on bioRxiv