The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15

  1. Shutoku Matsuyama
  2. Miyuki Kawase
  3. Naganori Nao
  4. Kazuya Shirato
  5. Makoto Ujike
  6. Wataru Kamitani
  7. Masayuki Shimojima
  8. Shuetsu Fukushi

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Abstract

Steroid compounds, which are expected to have dual functions in blocking host inflammation and MERS-CoV replication, were screened from a chemical library. Within this library, ciclesonide, an inhaled corticosteroid, suppressed human coronavirus replication in cultured cells, but did not suppress replication of respiratory syncytial virus or influenza virus. The effective concentration of ciclesonide to block SARS-CoV-2 (the cause of COVID-19) replication (EC 90 ) was 6.3 μM. After the eleventh consecutive MERS-CoV passage in the presence of ciclesonide, a resistant mutation was generated, which resulted in an amino acid substitution (A25V) in nonstructural protein (NSP) 15, as identified using reverse genetics. A recombinant virus with the mutation was also resistant to ciclesonide suppression of viral replication. These observations suggest that the effect of ciclesonide was specific to coronavirus, suggesting this is a candidate drug for treatment of patients suffering MERS or COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2020.03.11.987016: (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 and viruses: Vero cells and VeroE6 cells expressing TMPRSS2 (VeroE6/TMPRSS2) were maintained in Dulbecco’s modified Eagle medium (DMEM; Sigma-Aldrich, USA) supplemented with 5% fetal bovine serum (Gibco-BRL, USA).
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    MERS-CoV and SARS-CoV-2 were propagated in Vero and VeroE6/TMPRSS2 cells.
    VeroE6/TMPRSS2
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)

    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:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • 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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  2. Version published to 10.1101/2020.03.11.987016v1 on bioRxiv