In vitro screening of herbal medicinal products for their supportive curing potential in the context of SARS-CoV-2

  1. Hoai Thi Thu Tran
  2. Philipp Peterburs
  3. Jan Seibel
  4. D. Abramov-Sommariva
  5. Evelyn Lamy

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Abstract

Background

Herbal medicinal products have a long-standing history of use in the therapy of common respiratory infections. In the COVID-19 pandemic, they may have the potential for symptom relief in non-severe or moderate disease cases. Here we describe the results derived by in vitro screening of five herbal medicinal products with regard to their potential to i) interfere with the binding of the human Angiotensin-converting enzyme 2 (ACE2) receptor with the SARS-CoV-2 Spike S1 protein, ii) modulate the release of the human defensin HBD1 and cathelicidin LL-37 from human A549 lung cells upon Spike S1 protein stimulation and iii) modulate the release of IFN-γ from activated human peripheral blood mononuclear cells (PBMC). The investigated extracts were: Sinupret extract (SINx), Bronchipret thyme-ivy (BRO TE), Bronchipret thyme-primrose (BRO TP), Imupret (IMU), and Tonsipret (TOP).

Methods

The inhibitory effect of the herbal medicinal products on the binding interaction of Spike S1 protein and the human ACE2 receptor was measured by ELISA. The effects on intracellular IFN-γ expression in stimulated human PBMCs were measured by flow cytometry. Regulation on HBD1 and LL-37 expression and secretion was assessed in 25d long-term cultured human lung A549 epithelial cells by RT-PCR and ELISA.

Results

IMU and BRO TE concentration-dependently inhibited the interaction between spike protein and the ACE2 Receptor. However, this effect was only observed in the cell-free assay at a concentration range which was later on determined as cytotoxic to human PBMC. SINx, TOP and BRO TP significantly upregulated the intracellular expression of antiviral IFNγ from stimulated PBMC. Co-treatment of A549 cells with IMU or BRO TP together with SARS-CoV-2 spike protein significantly upregulated mRNA expression (IMU) and release (IMU and BRO TP) of HBD1 and LL-37 (BRO TP).

Conclusions

The in vitro screening results provide first evidence for an immune activating potential of some of the tested herbal medicinal extracts in the context of SARS-CoV-2. Whether these could be helpful in prevention of SARS-CoV-2 invasion or supportive in recovery from SARS-CoV-2 infection needs deeper understanding of the observations.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.01.433344: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: For PBMC isolation, blood was taken in Li-Heparin vacutainers from healthy volunteers at the University of Freiburg - Medical Center after written informed consent.
    IRB: The study was approved by the Ethics Committee of the University of Freiburg and carried out according to their guidelines and regulations (ethical vote 373/20).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Cells were then collected and processed for intracellular staining with anti-IFN-γ-FITC monoclonal antibody (Miltenyi Biotec, Germany).
    anti-IFN-γ-FITC
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Quantification of HBD1 and LL-37 peptide release from A549 cells: HBD1 and LL-37 peptide release was quantified in supernatants from 25 day long-term cultured A549 cells using a human BD-1 Standard ABTS ELISA Development Kit (PeproTech, Germany) and LL-37 human ELISA kit (HycultBiotech, Germany) according to the manufacturer’s instructions.
    A549
    suggested: None
    Software and Algorithms
    SentencesResources
    Assessment of SARS-CoV-2 Spike-ACE2 binding inhibition: The capacity of extracts to inhibit the SARS-CoV-2-Spike-ACE2 binding was tested using the SARS-CoV-2 (COVID-19) Inhibitor screening kit (BioCat GmbH, Heidelberg, Germany) according to the manufacturer’s instructions.
    BioCat
    suggested: (BioCAT, RRID:SCR_001440)
    Statistics: 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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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

    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.

  2. Version published to 10.1101/2021.03.01.433344v1 on bioRxiv