Discovery of a AHR pelargonidin agonist that counter-regulates Ace2 expression and attenuates ACE2-SARS-CoV-2 interaction

  1. Michele Biagioli
  2. Silvia Marchianò
  3. Rosalinda Roselli
  4. Cristina Di Giorgio
  5. Rachele Bellini
  6. Martina Bordoni
  7. Anna Gidari
  8. Samuele Sabbatini
  9. Daniela Francisci
  10. Bianca Fiorillo
  11. Bruno Catalanotti
  12. Eleonora Distrutti
  13. Adriana Carino
  14. Angela Zampella
  15. Gabriele Costantino
  16. Stefano Fiorucci

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

No abstract available

Article activity feed

  1. Version published to 10.1016/j.bcp.2021.114564
  2. ScreenIT

    SciScore for 10.1101/2021.02.24.432203: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Animals: All animal care and experimental procedures complied with the guidelines of Animal Care and were approved by Use Committee of the University of Perugia and by the Italian Minister of Health and Istituto Superiore di Sanità (Italy) and was in agreement with the European guidelines for use of experimental animals (permissions n. 583/2017-PR and 1126/2016-PR).
    Consent: An informed consent was obtained by each donor for the use of the plasma sample remnants and the protocol was approved by the Ethical Committee of the University of Perugia: authorization n. 61843 (July 13,2020).
    IRB: An informed consent was obtained by each donor for the use of the plasma sample remnants and the protocol was approved by the Ethical Committee of the University of Perugia: authorization n. 61843 (July 13,2020).
    RandomizationAfter 8 days, Ahr+/+ and Ahr−/− HFD-F mice were randomized to receive HFD-F alone or plus Pelargonidin (5 mg/Kg/die) by oral gavage for remaining 7 weeks.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableBriefly, according to this 8–10 weeks old male mice C57BL/6J wild-type and Ahr+/+ and Ahr−/− on C57BL/6J genetic background were administrated.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The program’s protocol included the quantitative analysis of the anti-SARS-CoV-2 IgG antibodies directed against the subunits (S1) and (S2) of the virus spike protein.
    anti-SARS-CoV-2 IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Transactivation Assay: For AhR-mediated transactivation, HepG2 cells were plated at 7.5 × 104 cells/well in a 24-well plate.
    HepG2
    suggested: None
    Cell culture: Caco-2 cells, a human intestinal epithelial cell line (Sigma-Aldrich) was grown at 37 °C in D-MEM containing 10% FBS, 1% l-glutamine, and 1% penicillin/streptomycin.
    Caco-2
    suggested: None
    SARS-CoV-2 yield reduction assay: Vero E6 cells (20,000 cells/well) were seeded in 96-well clear flat-bottom plates and incubated at 37°C with 5% CO2 for 24 h.
    Vero E6
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Mouse spleen macrophages purification: Spleens were collected from AhR+/+ and AhR−/− mice.
    AhR−/−
    suggested: None
    AhR knock out mice (Ahr−/−) on C57BL/6 background and their C57BL/6 congenic littermates wild type (Ahr+/+) were originally supplied by Charles River (Wilmington, MA, USA).
    C57BL/6
    suggested: None
    Briefly, according to this 8–10 weeks old male mice C57BL/6J wild-type and Ahr+/+ and Ahr−/− on C57BL/6J genetic background were administrated.
    C57BL/6J
    suggested: RRID:IMSR_JAX:000664)
    Software and Algorithms
    SentencesResources
    Primers were designed using the software PRIMER3 (http://frodo.wi.mit.edu/primer3/), using data published in the NCBI database.
    PRIMER3
    suggested: (Primer3, RRID:SCR_003139)
    NCBI
    suggested: (NCBI, RRID:SCR_006472)
    The receptor was treated with the Protein Preparation [34] tool implemented in Maestro ver.
    Maestro
    suggested: (Maestro, RRID:SCR_016748)
    The docking procedure was realized with the Glide software package (Glide, version 7.1.
    Glide
    suggested: (Glide, RRID:SCR_000187)

    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.
    • 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 10.1101/2021.02.24.432203v1 on bioRxiv