Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses

  1. Xi Yu
  2. Liming Zhang
  3. Liangqin Tong
  4. Nana Zhang
  5. Han Wang
  6. Yun Yang
  7. Mingyu Shi
  8. Xiaoping Xiao
  9. Yibin Zhu
  10. Penghua Wang
  11. Qiang Ding
  12. Linqi Zhang
  13. Chengfeng Qin
  14. Gong Cheng

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Abstract

Viruses are the major aetiological agents of acute and chronic severe human diseases that place a tremendous burden on global public health and economy; however, for most viruses, effective prophylactics and therapeutics are lacking, in particular, broad-spectrum antiviral agents. Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 ( Cb AE-1) and Cb AE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The Cb AEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation of Cb AE-1 in its lipase motif fully abrogated the virucidal ability. Furthermore, Cb AE-2 presented low toxicity in vivo and in vitro , highlighting its potential as a broad-spectrum antiviral drug.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.22.109900: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The collection of human blood samples and their use for mosquito feeding was approved by the local ethics committee at Tsinghua University.
    IACUC: The animal protocol used in this study was approved by the Institutional Animal Care and Use Committee of Tsinghua University and performed in accordance with their guidelines.
    RandomizationQuantification and Statistical Analysis: Animals were randomly allocated into different groups.
    BlindingThe investigators were not blinded to the allocation during the experiments or to the outcome assessment.
    Power Analysisnot detected.
    Sex as a biological variableMice, mosquitoes, cells, viruses and bacteria: Eight-week-old female ICR mice purchased from Vital River Laboratories in China were used for toxicity assay.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Vero cells, HEK-293T cells and A549 cells were maintained in Dulbecco’s modified Eagle’s medium (11965-092, Gibco) supplemented with 10% heat-inactivated foetal bovine serum (16000-044, Gibco) and 1% antibiotic-antimycotic (15240-062, Invitrogen) in a humidified 5% (V/V) CO2 incubator at 37°C.
    HEK-293T
    suggested: None
    Plaque reduction neutralization tests (PRNTs): Vero cells were seeded at ∼4×105 cells per well in 6-well plates and then incubated at 37°C overnight before reaching 80–90% confluence.
    Vero
    suggested: None
    SARS-CoV-2 pseudoviruses were purchased from GenScript, and neutralization activity was measured using the HEK-293T-ACE2 cell line with the same procedures as mentioned above.
    HEK-293T-ACE2
    suggested: None
    Cytotoxicity assay: The cytotoxicity of the CbAEs was evaluated in Vero cells and A549 cells.
    A549
    suggested: NCI-DTP Cat# A549, RRID:CVCL_0023)
    Software and Algorithms
    SentencesResources
    at the UniProt Database using Mascot software.
    Mascot
    suggested: (Mascot, RRID:SCR_014322)
    The half-lethal dose (LD50) was calculated using a sigmoidal nonlinear regression function to fit the dose-response curve in GraphPad Prism 8.0 (GraphPad Software, USA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    All analyses were performed using GraphPad Prism statistical software.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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.

    About SciScore

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  2. Version published to 10.1101/2020.05.22.109900v2 on bioRxiv
  3. Version published to 10.1101/2020.05.22.109900v1 on bioRxiv