Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mouse Models

  1. Yingjun Li
  2. Liu Cao
  3. Ge Li
  4. Feng Cong
  5. Yunfeng Li
  6. Jing Sun
  7. Yinzhu Luo
  8. Guijiang Chen
  9. Guanguan Li
  10. Ping Wang
  11. Fan Xing
  12. Yanxi Ji
  13. Jincun Zhao
  14. Yu Zhang
  15. Deyin Guo
  16. Xumu Zhang

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Abstract

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  1. Version published to 10.1021/acs.jmedchem.0c01929
  2. ScreenIT

    SciScore for 10.1101/2020.10.26.353300: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: All protocols were approved by the Animal Welfare Committee and all procedures used in this study complied with the guidelines and policies of the Animal Care and Use Committee.
    RandomizationImmediately, they were randomly divided into two groups (each group had 9 mice).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablePK analysis: SD rats (male, four animals per group) weighing 180–220 g were injected with GS-441514 intravenously (iv) and intragastricly (ig) at a dose of 30mg/kg.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Cells were then incubated with a rabbit anti-SARS-CoV-2 nucleocapsid protein polyclonal antibody (Cat. No.: 40143-T62, Sino Biological), followed by an HRP-labeled goat anti-rabbit secondary antibody (Cat. No.: 109-035-088, Jackson ImmunoResearch Laboratories).
    anti-SARS-CoV-2 nucleocapsid protein
    suggested: (Proteintech Cat# 80026-1-RR, RRID:AB_2882944)
    anti-rabbit
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Calu-3 cells were cultured in DMEM supplemented with 20% FBS, 100 U/mL penicillin and streptomycin, and 1% NEAA at 37 °C in a humidified atmosphere of 5% CO2.
    Calu-3
    suggested: None
    Antiviral activity assays: Vero E6, calu-3 and coco-2 cells were seeded at 1 × 105 cells per well in 24-well plates.
    coco-2
    suggested: None
    Lung homogenates were serially diluted and used to inoculate Vero E6 cells at 37°C for 1 h.
    Vero E6
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Vero-E6 and caco-2 were cultured in DMEM supplemented with 10% FBS, 100 U/mL penicillin and streptomycin at 37 °C in a humidified atmosphere of 5% CO2.
    Vero-E6
    suggested: None
    The modified intratracheal aerosolization was used to intratracheally delivery AAV vector (5×1011 GC) to lung tissue of 4-week-old BALB/c mice.35, 36 Briefly, mice were anesthetized with 2.5% isoflurane in O2 (1 L/min).
    BALB/c
    suggested: RRID:IMSR_ORNL:BALB/cRl)
    Software and Algorithms
    SentencesResources
    The dose-response curves were plotted from viral RNA copies versus the drug concentrations using GraphPad Prism 6 software. qRT-PCR analysis: For SARS-CoV-2 supernatant RNA quantification, RNA was isolated by E.Z.N.A.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Data analysis was performed with GraphPad Prism Software (GraphPad Software Inc.
    GraphPad
    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 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.

  3. Version published to 10.1101/2020.10.26.353300v1 on bioRxiv