Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture

  1. Kenneth H. Risner
  2. Katie V. Tieu
  3. Yafei Wang
  4. Michael Getz
  5. Allison Bakovic
  6. Nishank Bhalla
  7. Steven D. Nathan
  8. Daniel E. Conway
  9. Paul Macklin
  10. Aarthi Narayanan
  11. Farhang Alem

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Abstract

In an effort to identify therapeutic intervention strategies for the treatment of COVID-19, we have investigated a selection of FDA-approved small molecules and biologics that are commonly used to treat other human diseases. A investigation into 18 small molecules and 3 biologics was conducted in cell culture and the impact of treatment on viral titer was quantified by plaque assay. The investigation identified 4 FDA-approved small molecules, Maraviroc, FTY720 (Fingolimod), Atorvastatin and Nitazoxanide that were able to inhibit SARS-CoV-2 infection. Confocal microscopy with over expressed S-protein demonstrated that Maraviroc reduced the extent of S-protein mediated cell fusion as observed by fewer multinucleate cells in the context of drugtreatment. Mathematical modeling of drug-dependent viral multiplication dynamics revealed that prolonged drug treatment will exert an exponential decrease in viral load in a multicellular/tissue environment. Taken together, the data demonstrate that Maraviroc, Fingolimod, Atorvastatin and Nitazoxanide inhibit SARS-CoV-2 in cell culture.

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  1. Version published to 10.1101/2020.08.12.246389v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.08.12.246389: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    Inhibitors and Antibodies: Antibodies Eculizumab (HCA312), Bevacizumab (HCA182) and CD126/IL-6R (AHP2449) were obtained from Biorad.
    Antibodies
    suggested: None
    HCA312
    suggested: None
    CD126/IL-6R
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Plaque assay: Plaque assays were performed using Vero cells grown to a cell number of 2E5 cells/well in a 12-well plate.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    Images were analyzed by Fiji (U.S. National Institutes of Health, Bethesda,
    Fiji
    suggested: (Fiji, RRID:SCR_002285)

    Results from OddPub: Thank you for sharing your code.

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04435314Not yet recruitingEfficacy and Safety of Nitazoxanide for Post Exposure Prophy…
    NCT04288713AvailableEculizumab (Soliris) in Covid-19 Infected Patients
    NCT04435522CompletedMaraviroc in Patients With Moderate and Severe COVID-19
    NCT04280588WithdrawnFingolimod in COVID-19
    NCT04280588WithdrawnFingolimod in COVID-19
    NCT04380402Not yet recruitingAtorvastatin as Adjunctive Therapy in COVID-19

    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.
    • Thank you for including a protocol registration statement.

    About SciScore

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  3. Version published to 10.1101/2020.08.12.246389v1 on bioRxiv