PI3K/mTOR and topoisomerase inhibitors with potential activity against SARS-CoV-2 infection

  1. James Robert White
  2. Michael Bonner Foote
  3. Justin Jee
  4. Guillem Argilés
  5. Jonathan C.M. Wan
  6. Luis Alberto Diaz

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Abstract

There is an urgent need to identify therapies to prevent and treat SARS-CoV-2 infection. We performed a statistical evaluation of in vitro gene expression profiles reflecting exposure to 1,835 drugs, and found topoisomerase inhibitors and PI3K/mTOR pathway inhibitors among the strongest candidates for reduced expression of ACE2, a host gene associated with SARS-CoV-2 infection. Retrospective clinical data suggest that patients on these agents may be less likely to test positive for SARS-CoV-2.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.02.20186783: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study Approval: This study was approved by the Institutional Review Board at Memorial Sloan Kettering Cancer Center.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableAdditional study covariates (female gender, age greater than or equal to 65, non-white race, smoking, hematologic malignancy, metastatic disease) were similarly evaluated.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This study has several limitations. ACE2-associated antineoplastic therapies were discovered by in-vitro computer modeling and need to be validated experimentally. Although in vitro data implicates ACE2 in the SARS-CoV-2 infection route, ACE2 is not yet a clinically validated target. Furthermore, clinical data obtained were retrospective and may be underpowered to estimate the true impact of ACE2-associated therapy on SARS-CoV-2 positivity and COVID-19 adverse outcomes. Finally, study patient characteristics are skewed towards non-metastatic (63.2%), solid tumor (93.3%) patients. Despite these limitations, our results suggest that further investigation of PI3K/mTOR pathway inhibitors and topoisomerase inhibitors as a COVID-19 preventative strategy are warranted.

    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

    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.

  2. Version published to 10.1101/2020.09.02.20186783v1 on medRxiv