Ethacridine inhibits SARS-CoV-2 by inactivating viral particles in cellular models

  1. Xiaoquan Li
  2. Peter Lidsky
  3. Yinghong Xiao
  4. Chien-Ting Wu
  5. Miguel Garcia-Knight
  6. Junjiao Yang
  7. Tsuguhisa Nakayama
  8. Jayakar V. Nayak
  9. Peter K. Jackson
  10. Raul Andino
  11. Xiaokun Shu

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Abstract

SARS-CoV-2 is the coronavirus that causes the respiratory disease COVID-19, which is now the third-leading cause of death in the United States. The FDA has recently approved remdesivir, an inhibitor of SARS-CoV-2 replication, to treat COVID-19, though recent data from the WHO shows little to no benefit with use of this anti-viral agent. Here we report the discovery of ethacridine, a safe antiseptic use in humans, as a potent drug for use against SARS-CoV-2 (EC 50 ~ 0.08 μ M). Ethacridine was identified via high-throughput screening of an FDA-approved drug library in living cells using a fluorescent assay. Interestingly, the main mode of action of ethacridine is through inactivation of viral particles, preventing their binding to the host cells. Indeed, ethacridine is effective in various cell types, including primary human nasal epithelial cells. Taken together, these data identify a promising, potent, and new use of the old drug possessing a distinct mode of action for inhibiting SARS-CoV-2.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.28.359042: (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.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Immunostaining was further carried out using an antibody against nucleocapsid (Genetex, SARS-CoV-2 (COVID-19
    antibody against nucleocapsid ( Genetex , SARS-CoV-2
    suggested: None
    9) nucleocapsid antibody, GTX135357) or an antibody against spike (Genetex, SARS-CoV-2 (COVID-19) spike antibody [1A9], GTX632604) and visualized with goat anti-rabbit IgG H&L (Alexa Fluor® 488) (Abcam, ab150077) or goat anti-mouse IgG H&L (Alexa Fluor® 555) (Abcam, ab150114).
    GTX135357
    suggested: (GeneTex Cat# GTX135357, RRID:AB_2868464)
    GTX632604
    suggested: (GeneTex Cat# GTX632604, RRID:AB_2864418)
    anti-rabbit IgG
    suggested: (Abcam Cat# ab150077, RRID:AB_2630356)
    anti-mouse IgG
    suggested: (Abcam Cat# ab150114, RRID:AB_2687594)
    Experimental Models: Cell Lines
    SentencesResources
    To check the FlipGFPMpro signal after SARS-CoV-2 infection, HEK293T on 10-mm coverglasses were transfected with 200 ng of pcDNA3.1-hACE2 (Addgene, #145033) 24 hours later.
    HEK293T
    suggested: None
    Those 293T cells were further infected with SARS-CoV-2 at an MOI of 0.5.
    293T
    suggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)
    A clinical isolate of SARS-CoV-2 (USA-WA1/2020, BEI Cat No: NR-52281) was propagated in Vero E6 cells.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Images were acquired using Nikon Eclipse Ti-E Spinning Disk under 60X and processed in ImageJ.
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)
    Statistics: All statistics were performed in GraphPad Prism.
    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: 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 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: Please consider improving the rainbow (“jet”) colormap(s) used on page 12. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

  2. Version published to 10.1101/2020.10.28.359042 on bioRxiv