Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2

  1. Katie Heiser
  2. Peter F. McLean
  3. Chadwick T. Davis
  4. Ben Fogelson
  5. Hannah B. Gordon
  6. Pamela Jacobson
  7. Brett Hurst
  8. Ben Miller
  9. Ronald W. Alfa
  10. Berton A. Earnshaw
  11. Mason L. Victors
  12. Yolanda T. Chong
  13. Imran S. Haque
  14. Adeline S. Low
  15. Christopher C. Gibson

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Abstract

To identify potential therapeutic stop-gaps for SARS-CoV-2, we evaluated a library of 1,670 approved and reference compounds in an unbiased, cellular image-based screen for their ability to suppress the broad impacts of the SARS-CoV-2 virus on phenomic profiles of human renal cortical epithelial cells using deep learning. In our assay, remdesivir is the only antiviral tested with strong efficacy, neither chloroquine nor hydroxychloroquine have any beneficial effect in this human cell model, and a small number of compounds not currently being pursued clinically for SARS-CoV-2 have efficacy. We observed weak but beneficial class effects of β-blockers, mTOR/PI3K inhibitors and Vitamin D analogues and a mild amplification of the viral phenotype with β-agonists.

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  1. ScreenIT

    SciScore for 10.1101/2020.04.21.054387: (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

    Experimental Models: Cell Lines
    SentencesResources
    ” SARS-CoV-2 propagation and controls: The USA-WA1/2020 strain of SARS-CoV-2 was propagated in Vero 76 cells (ATCC CRL-1587).
    Vero 76
    suggested: None
    Viral inactivation in this sample was verified using visual CPE on Vero cells, where undetectable level of active virus was observed.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Caco-2 cells (HTB-37) were acquired from ATCC and propagated at 37°C with 5% CO2 in EMEM + 10% FBS.
    Caco-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Plates were imaged using Image Express Micro Confocal High-Content Imaging System (
    Image Express
    suggested: None

    Results from OddPub: Thank you for sharing your data.

    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.
    • No funding statement was detected.
    • 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 10.1101/2020.04.21.054387v1 on bioRxiv