In Vitro Effect of Taraxacum officinale Leaf Aqueous Extract on the Interaction between ACE2 Cell Surface Receptor and SARS-CoV-2 Spike Protein D614 and Four Mutants

  1. Hoai Thi Thu Tran
  2. Michael Gigl
  3. Nguyen Phan Khoi Le
  4. Corinna Dawid
  5. Evelyn Lamy

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Abstract

To date, there have been rapidly spreading new SARS-CoV-2 “variants of concern”. They all contain multiple mutations in the ACE2 receptor recognition site of the spike protein, compared to the original Wuhan sequence, which is of great concern, because of their potential for immune escape. Here we report on the efficacy of common dandelion (Taraxacum officinale) to block protein–protein interaction of SARS-COV-2 spike to the human ACE2 receptor. This could be shown for the wild type and mutant forms (D614G, N501Y, and a mix of K417N, E484K, and N501Y) in human HEK293-hACE2 kidney and A549-hACE2-TMPRSS2 lung cells. High-molecular-weight compounds in the water-based extract account for this effect. Infection of the lung cells using SARS-CoV-2 spike D614 and spike Delta (B.1.617.2) variant pseudotyped lentivirus particles was efficiently prevented by the extract and so was virus-triggered pro-inflammatory interleukin 6 secretion. Modern herbal monographs consider the usage of this medicinal plant as safe. Thus, the in vitro results reported here should encourage further research on the clinical relevance and applicability of the extract as prevention strategy for SARS-CoV-2 infection in terms of a non-invasive, oral post-exposure prophylaxis.

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  1. Version published to 10.3390/ph14101055
  2. ScreenIT

    SciScore for 10.1101/2021.03.19.435959: (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
    Cell lines and culture conditions: Human embryonic kidney 293 (HEK293) cells, stably expressing hACE2, were generously provided by Prof. Dr. Stefan Pöhlmann (Göttingen, Germany).
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)
    Human A549-hACE2-TMPRSS2 cells, generated from the human lung A549 cell line were purchased from InvivoGen SAS (Toulouse Cedex 4, France) and maintained in DMEM, high glucose supplemented with 10% heat-inactivated FCS, 100 U/ml penicillin/streptomycin, 100 µg/ml normocin, 0.5 µg/ml puromycin and 300 µg/ml hygromycin.
    A549
    suggested: None
    Infection of A549-hACE2-TMPRSS2 cells using SARS-CoV-2 pseudotyped lentivirus: SARS-CoV-2 spike pseudotyped lentivirus particles, produced with SARS-CoV-2 spike (Genbank Accession #QHD43416.1) as the envelope glycoproteins instead of the commonly used VSV-G, were purchased from BPS Bioscience, (Catalog#: 79942, Biomol, Hamburg).
    A549-hACE2-TMPRSS2
    suggested: None
    Software and Algorithms
    SentencesResources
    The cells were analysed by using a FACSCalibur (BD Biosciences, Heidelberg, Germany), 10.000 events were acquired.
    FACSCalibur
    suggested: None
    The median fluorescence intensity (MFI) of each sample were determined using FlowJo software (Ashland, Oregon, USA)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analysis: Results were analysed using the GraphPad Prism 6.0 software (La Jolla, California, USA).
    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 7. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

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

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.03.19.435959v1 on bioRxiv