The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model

  1. Rana Abdelnabi
  2. Caroline S. Foo
  3. Suzanne J.F. Kaptein
  4. Xin Zhang
  5. Thuc Nguyen Dan Do
  6. Lana Langendries
  7. Laura Vangeel
  8. Judith Breuer
  9. Juanita Pang
  10. Rachel Williams
  11. Valentijn Vergote
  12. Elisabeth Heylen
  13. Pieter Leyssen
  14. Kai Dallmeier
  15. Lotte Coelmont
  16. Arnab K. Chatterjee
  17. Raf Mols
  18. Patrick Augustijns
  19. Steven De Jonghe
  20. Dirk Jochmans
  21. Birgit Weynand
  22. Johan Neyts

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Abstract

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  1. Version published to 10.1016/j.ebiom.2021.103595
  2. Version published to 10.1101/2020.12.10.419242v5 on bioRxiv
  3. Version published to 10.1101/2020.12.10.419242v4 on bioRxiv
  4. Version published to 10.1101/2020.12.10.419242v3 on bioRxiv
  5. Version published to 10.1101/2020.12.10.419242v2 on bioRxiv
  6. ScreenIT

    SciScore for 10.1101/2020.12.10.419242: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Housing conditions and experimental procedures were approved by the ethics committee of animal experimentation of KU Leuven (license P065-2020).
    Randomizationnot detected.
    BlindingTissue sections (5 μm) were analyzed after staining with hematoxylin and eosin and scored blindly for lung damage by an expert pathologist.
    Power Analysisnot detected.
    Sex as a biological variableFemale hamsters of 6-8 weeks old were anesthetized with ketamine/xylazine/atropine and inoculated intranasally with 50 μL containing 2×106 TCID50 SARS-CoV-2 (day 0).
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Vero E6 cells (African green monkey kidney, ATCC CRL-1586) were cultured in minimal essential medium (Gibco) supplemented with 10% fetal bovine serum (Integro), 1% L-glutamine (Gibco) and 1% bicarbonate (Gibco).
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Reads generated were trimmed with Trim Galore (https://github.com/FelixKrueger/TrimGalore).
    Trim Galore
    suggested: (Trim Galore, RRID:SCR_011847)
    Duplicated reads were removed using Picard (http://broadinstitute.github.io/picard).
    Picard
    suggested: (Picard, RRID:SCR_006525)
    Reads from the inoculation sample were mapped to the SARS-CoV-2 reference genome (NC_045512) from GenBank using BWA-MEM (16).
    BWA-MEM
    suggested: (Sniffles, RRID:SCR_017619)
    The mapping quality was checked using Qualimap and the consensus whole genome sequence was generated using QUASR (17, 18).
    Qualimap
    suggested: (QualiMap, RRID:SCR_001209)
    Variants above 1% and with a minimum of 2 supporting reads per strand were identified at sites with a read depth of ≥ 10 using VarScan (19).
    VarScan
    suggested: (VARSCAN, RRID:SCR_006849)
    Statistics: GraphPad Prism (GraphPad Software, Inc.) was used to perform statistical analysis.
    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04405570CompletedA Safety, Tolerability and Efficacy of Molnupiravir (EIDD-28…
    NCT04405739RecruitingThe Safety of Molnupiravir (EIDD-2801) and Its Effect on Vir…

    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.

  7. Version published to 10.1101/2020.12.10.419242v1 on bioRxiv