Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

  1. Jean-Sélim Driouich
  2. Maxime Cochin
  3. Guillaume Lingas
  4. Grégory Moureau
  5. Franck Touret
  6. Paul-Rémi Petit
  7. Géraldine Piorkowski
  8. Karine Barthélémy
  9. Caroline Laprie
  10. Bruno Coutard
  11. Jérémie Guedj
  12. Xavier de Lamballerie
  13. Caroline Solas
  14. Antoine Nougairède

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Abstract

Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment is initiated before or simultaneously to infection, favipiravir has a strong dose effect, leading to reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlates with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. Antiviral efficacy is achieved with plasma drug exposure comparable with those previously found during human clinical trials. Notably, the highest dose of favipiravir tested is associated with signs of toxicity in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.

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  1. Version published to 10.1038/s41467-021-21992-w
  2. Version published to 10.1101/2020.07.07.191775v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.07.07.191775: (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
    Cells: VeroE6 cells (ATCC CRL-1586) and Caco-2 cells (ATCC HTB-37) were grown at 37°C with 5% CO2 in minimal essential medium (MEM) supplemented with 7.5% heat-inactivated fetal bovine serum (FBS), 1% Penicillin/Streptomycin and 1% non-essential amino acids (all from ThermoFisher Scientific).
    VeroE6
    suggested: None
    Caco-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Graphical representations and statistical analyses were performed with Graphpad Prism 7 (Graphpad software) except linear/nonlinear regressions and their corresponding graphical representations that were performed using R statistical software (http://www.R-project.org).
    Graphpad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Graphpad
    suggested: (GraphPad, RRID:SCR_000306)

    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: 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.

  4. Version published to 10.1101/2020.07.07.191775v1 on bioRxiv