Copper(II) Gluconate Boosts the Anti-SARS-CoV-2 Effect of Disulfiram In Vitro

  1. Luyan Xu
  2. Wei Xu
  3. Simeng Zhao
  4. Suwen Zhao
  5. Lu Lu
  6. Bo-Lin Lin

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Abstract

Disulfiram is a 70-year-old anti-alcoholism drug, while copper(II) gluconate (Cu(Glu) 2 ) is a commonly used food additive or copper supplement. Here we disclose that the combination of disulfiram and copper(II) gluconate drastically enhances the anti-SARS-CoV-2 activity at the cellular level as compared to disulfiram or copper(II) gluconate alone. A 1:1 mixture of disulfiram and copper(II) gluconate shows an EC 50 value of 154 nM against SARS-CoV-2 at the cellular level, much lower than the 17.45 μM reported for disulfiram alone. Notably, previous clinical trials have shown that a combination of 250 mg disulfiram (0.843 mmol) and 8 mg copper(II) gluconate (0.0176 mmol) oral capsules per day is well tolerated ( NCT03034135 , NCT00742911 ). A preliminary mechanism is proposed to rationalize the observed promotional effect.

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  1. Version published to 10.1101/2021.09.17.460613v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.09.17.460613: (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.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    The virus was purified by phagocytosis, reproduced in Vero-E6 cells, and stored in -80 °C for future use.
    Vero-E6
    suggested: None

    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: 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

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  3. Version published to 10.1101/2021.09.17.460613v1 on bioRxiv