Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants

  1. Katherine E. Zarn
  2. Sierra A. Jaramillo
  3. Anthony R. Zapata
  4. Nathan E. Stone
  5. Ashley N. Jones
  6. Haley E. Nunnally
  7. Erik W. Settles
  8. Ken Ng
  9. Paul S. Keim
  10. Steen Knudsen
  11. Patricia M. Nuijten
  12. Aloys S. L. Tijsma
  13. Christopher T. French

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Abstract

We recently published a preliminary assessment of the activity of a poly (ADP-ribose) polymerase (PARP) inhibitor, stenoparib, also known as 2X-121, which inhibits viral replication by affecting pathways of the host. Here we show that stenoparib effectively inhibits a SARS-CoV-2 wild type (BavPat1/2020) strain and four additional variant strains; alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2) and gamma (P.1) in vitro , with 50% effective concentration (EC 50 ) estimates of 4.1 μM, 8.5 μM, 24.1 μM, 8.2 μM and 13.6 μM, respectively. A separate experiment focusing on a combination of 10 μM stenoparib and 0.5 μM remdesivir, an antiviral drug, resulted in over 80% inhibition of the alpha variant, which is substantially greater than the effect achieved with either drug alone, suggesting at least additive effects from combining the different mechanisms of activity of stenoparib and remdesivir.

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  1. Version published to 10.1371/journal.pone.0272916
  2. Version published to 10.1101/2021.11.03.467186v3 on bioRxiv
  3. Version published to 10.1101/2021.11.03.467186v4 on bioRxiv
  4. Version published to 10.1101/2021.11.03.467186v2 on bioRxiv
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    SciScore for 10.1101/2021.11.03.467186: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot 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 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.

    Results from scite Reference Check: We found no unreliable references.

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  6. Version published to 10.1101/2021.11.03.467186v1 on bioRxiv