The Natural Stilbenoid (–)-Hopeaphenol Inhibits Cellular Entry of SARS-CoV-2 USA-WA1/2020, B.1.1.7, and B.1.351 Variants

  1. Ian Tietjen
  2. Joel Cassel
  3. Emery T. Register
  4. Xiang Yang Zhou
  5. Troy E. Messick
  6. Frederick Keeney
  7. Lily D. Lu
  8. Karren D. Beattie
  9. Topul Rali
  10. Pablo Tebas
  11. Hildegund C. J. Ertl
  12. Joseph M. Salvino
  13. Rohan A. Davis
  14. Luis J. Montaner

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Abstract

Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host angiotensin-converting enzyme II (ACE2) receptor may be effective inhibitors of SARS-CoV-2 cell entry.

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  1. Version published to 10.1128/aac.00772-21
  2. ScreenIT

    SciScore for 10.1101/2021.04.29.442010: (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.
    BlindingCells were incubated for an additional 4 days, at which point all wells were scored for the presence of CPE by a user blinded to the identity of the wells.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Pseudoviruses were generated in BHK-21/WI-2 cells using a pseudotyped ΔG-GFP (G*ΔG-GFP) rVSV (Kerafast, Boston, MA, USA) in addition to spike sequences cloned into the paT7- Spike plasmid as described previously (21).
    BHK-21/WI-2
    suggested: RRID:CVCL_HB78)
    Viral CPE assays: Vero-E6 cells were plated in D10+ to 20,000 cells per well in 96-well format and incubated for 24 hours.
    Vero-E6
    suggested: None
    Recombinant DNA
    SentencesResources
    Generation of Mpro protein: The codon-optimized gene for SARS-CoV-2 Mpro (or 3CLpro) (GenBank: QHD43415.1 aa 3264-3567) from strain BetaCoV/Wuhan/WIV04/2019 was ordered from IDT (Coralville, IA, USA) and cloned into a HIS-SUMO expression vector (a modified pET-DUET; Novagen, Madison, WI, USA).
    pET-DUET
    suggested: RRID:Addgene_111354)
    Software and Algorithms
    SentencesResources
    Data analysis: For all studies, 50% effective concentrations were calculated using nonlinear regression of a one-side binding model using GraphPad Prism v. 8.4.3 (GraphPad, San Diego, CA, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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.

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

    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.

  3. Version published to 10.1101/2021.04.29.442010v1 on bioRxiv