Resveratrol And Pterostilbene Potently Inhibit SARS-CoV-2 Replication In Vitro

  1. Bram M. ter Ellen
  2. Nilima Dinesh Kumar
  3. Ellen M. Bouma
  4. Berit Troost
  5. Denise P.I. van de Pol
  6. Heidi H. van der Ende-Metselaar
  7. Leonie Apperloo
  8. Djoke van Gosliga
  9. Maarten van den Berge
  10. Martijn C. Nawijn
  11. Peter H.J. van der Voort
  12. Jill Moser
  13. Izabela A. Rodenhuis-Zybert
  14. Jolanda M. Smit

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Abstract

The current COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has an enormous impact on human health and economy. In search for therapeutic options, researchers have proposed resveratrol, a food supplement with known antiviral, anti-inflammatory and anti-oxidant properties as an advantageous antiviral therapy for SARS-CoV-2 infection. Here, we provide evidence that both resveratrol and its metabolically more stable structural analog, pterostilbene, exhibit potent antiviral properties against SARS-CoV-2 in vitro . Resveratrol and pterostilbene showed antiviral activity in African green monkey kidney cells and in human primary bronchial epithelial cells cultured in an air-liquid interface system. Both compounds actively inhibit virus replication within infected cells as reduced virus progeny production was observed when the compound was added at post-inoculation conditions. Without replenishment of the compound, antiviral activity was observed up to roughly 5 rounds of replication, demonstrating the long-lasting effect of these compounds. Collectively, our data indicate that resveratrol and pterostilbene are promising antiviral compounds to treat SARS-CoV-2 infection. Because these results represent laboratory findings in cells, we advocate evaluation of these compounds in clinical trials before statements are made whether or not these drugs are advantageous for COVID-19 treatment.

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  1. Version published to 10.1101/2020.09.24.285940v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.09.24.285940: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The medical ethics committee of the University Medical Center Groningen approved the study, and all subjects gave their written informed consent.
    Consent: The medical ethics committee of the University Medical Center Groningen approved the study, and all subjects gave their written informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe donors were 2 male and 2 female non-smoking healthy control volunteers (less than 2.5 packyears) with no history of respiratory disease aged 49-62.
    Cell Line AuthenticationContamination: All cells were mycoplasma negative and maintained at 37°C under 5% CO2.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    The human lung epithelial cell line Calu-3 (ATCC HTB-55) was maintained in DMEM F-12 (Lonza) supplemented with 10% FBS, 1% Glutamax (Thermofisher), 1% non-essential amino acid (Thermofisher), penicillin (100 U/mL), and streptomycin (100 U/mL).
    Calu-3
    suggested: ATCC Cat# HTB-55, RRID:CVCL_0609)
    The original stock was passaged twice in Vero E6 cells to obtain a working stock.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    The human lung epithelial cell line Calu-3 (ATCC HTB-55) was maintained in DMEM F-12 (Lonza) supplemented with 10% FBS, 1% Glutamax (Thermofisher), 1% non-essential amino acid (Thermofisher), penicillin (100 U/mL), and streptomycin (100 U/mL).
    Thermofisher
    suggested: (ThermoFisher; SL 8; Centrifuge, RRID:SCR_020809)
    All data was analyzed in GraphPad Prism 8 software.
    GraphPad Prism
    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

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  3. Version published to 10.1101/2020.09.24.285940v1 on bioRxiv