Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine, and Pyronaridine: In Vitro Activity against SARS-CoV-2 and Potential Mechanisms

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Abstract

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  1. SciScore for 10.1101/2020.12.01.407361: (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

    No key resources detected.


    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:
    Despite this limitation, valuable information about the virus infection and replication can be learned from studies using these cell lines. A previous study (Chu et al., 2020) assessed 25 cell lines derived from different tissues or organs and host species and reported that cytopathic effects were only seen in VeroE6 and FRhK4 cells after SARS-CoV-2 inoculation for up to 120 hpi. These findings are important for optimization of antiviral assays based on cell protection assessment, because cell lines without obvious cytopathic effects might lead to overestimation of cell viability and drug efficacy (Chu et al., 2020). For efficient SARS-CoV-2 research, a cell line, such as Vero cells, that can easily replicate and isolate the virus is essential, but they have been shown not to produce interferon (IFN) when infected with Newcastle disease virus, rubella virus, and other viruses (Desmyter et al., 1968). Under previously described experimental conditions, productive SARS-CoV-2 replication in A549 cells was erratic (Sacramento et al., 2020) which can be overcome by preparing A549 cells overexpressing ACE2 (as used in the current study). The differences in responses in different cell lines could be accounted for by the basic biochemistry, for example hepatic cells, like Huh-7, are equipped with enzymes to synthesize nucleotides, carbohydrates and lipids (Nwosu et al., 2018). Hence it is not surprising that the highest potency of remdesivir against SARS-CoV-2 is found in Huh-7 cells...

    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.

    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.