Discovery of SARS-CoV-2 Papain-like Protease Inhibitors through a Combination of High-Throughput Screening and a FlipGFP-Based Reporter Assay

  1. Chunlong Ma
  2. Michael Dominic Sacco
  3. Zilei Xia
  4. George Lambrinidis
  5. Julia Alma Townsend
  6. Yanmei Hu
  7. Xiangzhi Meng
  8. Tommy Szeto
  9. Mandy Ba
  10. Xiujun Zhang
  11. Maura Gongora
  12. Fushun Zhang
  13. Michael Thomas Marty
  14. Yan Xiang
  15. Antonios Kolocouris
  16. Yu Chen
  17. Jun Wang

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Abstract

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  1. Version published to 10.1021/acscentsci.1c00519
  2. ScreenIT

    SciScore for 10.1101/2021.03.15.435551: (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, isolate USA-WA1/2020 (NR-52281), was obtained through BEI Resources and propagated once on VERO E6 cells before it was used for this study.
    VERO E6
    suggested: RRID:CVCL_XD71)
    For transfection, 96-well Greiner plate (Cat # 655090) was seeded with 293T cells to overnight 70-90% confluency.
    293T
    suggested: None
    4,28 Briefly, Vero E6 cells or Caca2-hACE2 cells in 96-well plates (Corning) were infected with SARS-CoV-2 (USA-WA1/2020 isolate) at a MOI of 0.1 in DMEM supplemented with 1% FBS.
    Caca2-hACE2
    suggested: None
    Software and Algorithms
    SentencesResources
    Images were acquired 2 days after transfection with Cytation 5 imaging reader (Biotek) GFP and mCherry channels; and were analyzed with Gen5 3.10 software (
    Gen5
    suggested: (Gen5, RRID:SCR_017317)
    30,31 Rigid and restrained refinements were performed using REFMAC and model building was performed with COOT.
    REFMAC
    suggested: (Refmac, RRID:SCR_014225)
    COOT
    suggested: (Coot, RRID:SCR_014222)
    32,33 Protein structure figures were made using PyMOL (Schrödinger, LLC).
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)

    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 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.
    • 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.

  3. Version published to 10.1101/2021.03.15.435551v1 on bioRxiv