Allicin inhibits SARS-CoV-2 replication and abrogates the antiviral host response in the Calu-3 proteome

  1. Kirstin Mösbauer
  2. Verena Nadin Fritsch
  3. Lorenz Adrian
  4. Jörg Bernhardt
  5. Martin Clemens Horst Gruhlke
  6. Alan John Slusarenko
  7. Daniela Niemeyer
  8. Haike Antelmann

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Abstract

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic is a major health burden. Volatile garlic organosulfur compounds, such as the thiol-reactive allicin (diallyl thiosulfinate) exert strong antimicrobial activity against various respiratory pathogens. Here, we investigated the antiviral activity of allicin against SARS-CoV-2 in infected Vero E6 and Calu-3 lung cells. Calu-3 cells showed greater allicin tolerance due >4-fold increased GSH levels compared to Vero E6. However, biocompatible allicin doses efficiently inhibited viral replication in both cell lines. Proteome analyses of SARS-CoV-2 infected Calu-3 cells revealed a strong induction of the antiviral interferon-stimulated gene (ISG) signature (e.g. cGAS, Mx1, IFIT, IFIH, IFI16, IFI44, 2’5’OAS and ISG15), pathways of vesicular transport, tight junctions (KIF5A/B/C, OSBPL2, CLTC1, ARHGAP17) and ubiquitin modification (UBE2L3/5), as well as reprogramming of host metabolism, transcription and translation. Allicin abrogated the ISG host response and reverted the host cellular pathways to levels of uninfected Calu-3 cells, confirming the antiviral and immunomodulatory activity of allicin in the host proteome. Thus, biocompatible doses of allicin could be promising for protection of lung cells against SARS-CoV-2.

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  1. Version published to 10.1101/2021.05.15.444275v2 on bioRxiv
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    SciScore for 10.1101/2021.05.15.444275: (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.
    Cell Line AuthenticationContamination: Cell lines were free of mycoplasma, authenticated based on morphology and growth properties and confirmed by PCR.
    Authentication: Cell lines were free of mycoplasma, authenticated based on morphology and growth properties and confirmed by PCR.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cultivation of cell lines and infection experiments with SARS-CoV-2: Vero E6 (ATCC CRL-1586) and Calu-3 (ATCC
    Vero E6
    suggested: None
    The peptide samples of non-infected Calu-3 cells (Mock) and SARS-CoV-2 infected Calu-3 cells with and without allicin treatment were subjected to nLC-MS/MS analysis using an Orbitrap Fusion (Thermo Fisher Scientific) coupled to a TriVersa NanoMate (Advion, Ltd.) as described previously [31].
    Calu-3
    suggested: KCLB Cat# 30055, RRID:CVCL_0609)
    Software and Algorithms
    SentencesResources
    Peptide identification of the human and SARS-CoV-2 proteome was performed by Proteome Discoverer (version 2.2, Thermo Fisher Scientific) using the SequestHT search engine as described [32].
    Proteome Discoverer
    suggested: (Proteome Discoverer, RRID:SCR_014477)
    Human and SARS-CoV-2 proteins were identified by searching all tandem MS/MS spectra against the human proteome protein sequence database (20286 entries) extracted from UniprotKB release 12.7 (Uniprot Consortium
    UniprotKB
    suggested: (UniProtKB, RRID:SCR_004426)
    The mass spectrometry data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository [33, 34] with the dataset identifier PXD024375.
    PRIDE
    suggested: (Pride-asap, RRID:SCR_012052)

    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.

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

    About SciScore

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  3. Version published to 10.1101/2021.05.15.444275v1 on bioRxiv