Nelfinavir markedly improves lung pathology in SARS-CoV-2-infected Syrian hamsters despite lack of an antiviral effect

  1. Caroline S. Foo
  2. Rana Abdelnabi
  3. Suzanne J. F. Kaptein
  4. Xin Zhang
  5. Sebastiaan ter Horst
  6. Raf Mols
  7. Leen Delang
  8. Joana Rocha-Pereira
  9. Lotte Coelmont
  10. Pieter Leyssen
  11. Kai Dallmeier
  12. Valentijn Vergote
  13. Elisabeth Heylen
  14. Laura Vangeel
  15. Arnab K. Chatterjee
  16. Pieter Annaert
  17. Patrick Augustijns
  18. Steven De Jonghe
  19. Dirk Jochmans
  20. Birgit Weynand
  21. Johan Neyts

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Abstract

In response to the ongoing COVID-19 pandemic, repurposing of drugs for the treatment of SARS-CoV-2 infections is being explored. The HIV protease inhibitor Nelfinavir, widely prescribed in combination with other HIV inhibitors, has been shown to inhibit in vitro SARS-CoV-2 replication. We here report on the effect of Nelfinavir in the Syrian hamster SARS-CoV-2 infection model. Although treatment of infected hamsters with either 15 or 50 mg/kg BID Nelfinavir [for four consecutive days, initiated on the day of infection] does not reduce viral RNA loads nor infectious virus titres in the lungs compared to the vehicle control, the drug reduced virus-induced lung pathology to nearly the baseline scores of healthy animals. A substantial interstitial infiltration of neutrophils is observed in the lungs of treated (both infected and uninfected) animals. The protective effect of Nelfinavir on SARS-CoV-2-induced lung pathology (at doses that are well tolerated and that result in exposures nearing those observed in HIV-infected patients) may lay the foundation for clinical studies with this widely used drug.

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  1. Version published to 10.1101/2021.02.01.429108v3 on bioRxiv
  2. Version published to 10.1101/2021.02.01.429108v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.02.01.429108: (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.

    Table 2: Resources

    No key resources detected.

    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 scite Reference Check: We found no unreliable references.

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  4. Version published to 10.1101/2021.02.01.429108v1 on bioRxiv