Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

  1. Adriana Carino
  2. Federica Moraca
  3. Bianca Fiorillo
  4. Silvia Marchianò
  5. Valentina Sepe
  6. Michele Biagioli
  7. Claudia Finamore
  8. Silvia Bozza
  9. Daniela Francisci
  10. Eleonora Distrutti
  11. Bruno Catalanotti
  12. Angela Zampella
  13. Stefano Fiorucci

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Abstract

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  1. Version published to 10.3389/fchem.2020.572885
  2. ScreenIT

    SciScore for 10.1101/2020.06.10.144964: (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.

    Table 2: Resources

    Antibodies
    SentencesResources
    Quantitative analysis of the anti-SARS-CoV-2 IgG antibodies: Remnant serum samples from post COVID-19 subjects were used.
    anti-SARS-CoV-2 IgG
    suggested: None
    subjects were plasma donors and we The quantitative analysis of the anti-SARS-CoV-2 IgG antibodies directed against the subunits (S1) and (S2) of the virus spike protein were measured by chemiluminescence immunoassay (CLIA) technology (LIAISON®SARS-CoV-2 IgG kit, DiaSorin®, Saluggia, Italy) in serum from COVID-19 PCR-confirmed cases (n = 5) who have recovered from coronavirus disease 2019 (COVID-19) in Italy.
    LIAISON®SARS-CoV-2 IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    The library of FDA approved drugs has been obtained both from DrugBank (2106 compounds) (Drugbank, 2020) and from the Selleckchem website (FDA-approved Drug Library, 2020) (tot. 2638).
    DrugBank
    suggested: (DrugBank, RRID:SCR_002700)
    Each database was converted to 3D and prepared with the LigPrep tool (Schröedinger, 2019) considering a protonation state at a physiological pH of 7.4.
    LigPrep
    suggested: (Ligprep, RRID:SCR_016746)

    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: We detected the following sentences addressing limitations in the study:
    This study has several limitations. First of all, we have observed that anti-adhesive effects exerted by hyperimmune plasma obtained from patients who have recovered from COVID-19, who have high titles of neutralizing antibodies, inhibit the Spike RBD/ACE2 interaction to a percentage close to 99%. This percentage is significantly higher than what we have measured with G-UDCA, the agent that gives the better results in this study. This suggests that small molecules binding of the hydrophobic pockets are less effective than a neutralizing antibody. This suggest that our pharmacological approach will likely be poorly effective in the presence of a highly replicative viral load. This also suggest that this approach might have some efficacy in preventing virus entry only in the case of low viral load. Nevertheless, the mild inhibition efficacy showed by c bile acids and their derivatives could pave the way for a further optimization of the binding mode exploring the chemical space of the steroidal nucleus in order to envisage additional potential interactions in pocket 5, recently demonstrated the least exposed to mutations in different circulating viral lineages. Another limitation is that we have not tested the effect of these treatment on viral replication and further studies are needed to clarify this point. In conclusion, in this paper, we have developed a strategy to target the interaction of SARS-CoV-2 S protein RBD with ACE2 receptor in identifying several steroidal deriva...

    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.

  3. Version published to 10.1101/2020.06.10.144964v1 on bioRxiv