TMPRSS2 and RNA-dependent RNA polymerase are effective targets of therapeutic intervention for treatment of COVID-19 caused by SARS-CoV-2 variants (B.1.1.7 and B.1.351)

  1. Jihye Lee
  2. JinAh Lee
  3. Hyeon Ju Kim
  4. Meehyun Ko
  5. Youngmee Jee
  6. Seungtaek Kim

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Abstract

SARS-CoV-2 is a causative agent of COVID-19 pandemic and the development of therapeutic interventions is urgently needed. So far, monoclonal antibodies and drug repositioning are the main methods for drug development and this effort was partially successful. Since the beginning of COVID-19 pandemic, the emergence of SARS-CoV-2 variants has been reported in many parts of the world and the main concern is whether the current vaccines and therapeutics are still effective against these variant viruses. The viral entry and viral RNA-dependent RNA polymerase (RdRp) are the main targets of current drug development, thus the inhibitory effects of TMPRSS2 and RdRp inhibitors were compared among the early SARS-CoV-2 isolate (lineage A) and the two recent variants (lineage B.1.1.7 and lineage B.1.351) identified in the UK and South Africa, respectively. Our in vitro analysis of viral replication showed that the drugs targeting TMPRSS2 and RdRp are equally effective against the two variants of concern.

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  1. ScreenIT

    SciScore for 10.1101/2021.04.06.438540: (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

    Antibodies
    SentencesResources
    Anti‐SARS‐CoV‐2 N protein antibody was purchased from Sino Biological Inc (Beijing, China)
    Anti‐SARS‐CoV‐2 N protein antibody
    suggested: None
    Anti‐SARS‐CoV‐2 N protein
    suggested: None
    Alexa Fluor 488 goat anti‐rabbit IgG (H + L) secondary antibody and Hoechst 33342 were purchased from Molecular Probes.
    Alexa Fluor 488 goat anti‐rabbit IgG
    suggested: None
    anti‐rabbit IgG
    suggested: None
    Anti-SARS-CoV-2 nucleocapsid (N) primary antibody, 488-conjugated goat anti-rabbit IgG secondary antibody and Hoechst 33342 were treated to the cells for immunofluorescence.
    Anti-SARS-CoV-2 nucleocapsid (N)
    suggested: None
    anti-rabbit IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus and cells: Vero and Vero E6 cells were obtained from the American Type Culture Collection (ATCC CCL-81 and C1008, respectively) and maintained at 37°C with 5% CO2 in Dulbecco’s modified Eagle’s medium (DMEM; Welgene), supplemented with 10% heat-inactivated fetal bovine serum (FBS) and 2% antibiotic-antimycotic solution (Gibco).
    Vero E6
    suggested: None
    Calu-3 cells were seeded at 2.0 × 104cells per well with Eagle’s Minimum Essential Medium (EMEM, ATCC) supplemented with 20% heat-inactivated fetal bovine serum (FBS), 1%
    Calu-3
    suggested: None
    For viral infection, plates were transferred into the BSL‐3 containment facility and SARS‐CoV‐2 was added at a multiplicity of infection of 0.008 for Vero cells and 0.2 for Calu-3 cells.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Software and Algorithms
    SentencesResources
    DRCs were generated using Prism7 software (GraphPad).
    GraphPad
    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

    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 10.1101/2021.04.06.438540 on bioRxiv