Zinc pyrithione is a potent inhibitor of PL Pro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication

  1. Jerneja Kladnik
  2. Ana Dolinar
  3. Jakob Kljun
  4. David Perea
  5. Judith Grau-Expósito
  6. Meritxell Genescà
  7. Marko Novinec
  8. Maria J. Buzon
  9. Iztok Turel

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Abstract

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  1. Version published to 10.1080/14756366.2022.2108417
  2. ScreenIT

    SciScore for 10.1101/2022.03.03.482819: (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.

    Table 2: Resources

    Recombinant DNA
    SentencesResources
    68 Recombinant PLPro was prepared according to the modified protocol.69 Briefly, the sequence was codon optimized, synthesized and cloned into pET28b/32 (pET28b with ampicillin resistance) using AcoI and XhoI sites.
    pET28b/32
    suggested: None
    Software and Algorithms
    SentencesResources
    Data were analysed and visualized in GraphPad Prism 9.
    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: We detected the following sentences addressing limitations in the study:
    However, the results are not clinically applicable due to various limitations of the study.49 On the other hand, an ongoing clinical trial of intravenous administration of ZnCl2 has so far confirmed its safe use and shown an increase in serum zinc levels.50,51 However, oral administration of the drug is much more patient-friendly and is preferred over intravenous use. Ionophores, molecules that enable the transport of metal ions across a lipid cell membrane, increase zinc uptake and facilitate zinc absorption, thus combating COVID-19.13,52–54 In a multi-center study testing zinc sulphate and hydroxychloroquine as potential treatments, increased hospital discharge and decreased in-hospital mortality were observed.55 However, hydroxychloroquine as a therapeutic against COVID-19 should be considered with great caution as it may significantly increase the risk of cardiac arrhythmias. Similarly, a high risk of cardiac dysfunction has been reported for chloroquine.56–58 Therefore, the choice of an appropriate chelating agent for zinc is of utmost importance. Pyrithione a is a known ionophore with the ability to bind zinc ions, increase their intracellular concentration59 and as such has recognized antiviral activity against Coronavirus (SARS-CoV), Arterivirus, Coxsackievirus, Mengovirus, Picornavirus and Rhinovirus.60 A decade ago, te Velthius et al. demonstrated that the combination of Zn2+ ions and pyrithione a effectively inhibited the replication of SARS-CoV via Zn2+ suppressio...

    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

    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 10.1101/2022.03.03.482819v1 on bioRxiv