Discovery of rhodomyrtone as a broad-spectrum antiviral inhibitor with anti-SARS-CoV-2 activity
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Abstract
The outbreak of new viruses, such as serve acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as the emerging of drug-resistance viruses highlight the urgent need for the development of broad-spectrum antiviral drugs. Herein, we report the discovery of a plant-derived small molecule, 6,8-dihydroxy-9-isobutyl-2,2,4,4-tetramethyl-7-(3-methylbutanoyl)-4,9-dihydro-1 H -xanthene-1,3(2 H )-dione (rhodomyrtone, RDT), which exhibited potent broad-spectrum antiviral activities against several RNA and DNA viruses, including SARS-CoV-2, respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and Kaposi’s sarcoma-associated herpesvirus (KSHV). RDT can significantly suppress viral gene expression and show the low possibility to elicit drug-resistant variants. Mechanistic study implied that RDT inhibited viral infection by disturbing the cellular factors that essential for viral gene expression. Our results suggested that RDT might be a promising lead compound for the development of broad-spectrum antiviral drugs.
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SciScore for 10.1101/2020.11.14.382770: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The cells were then washed with PBS twice, blocked by 5% BSA and incubated with mouse anti-HSV-1 gD monoclonal antibody (1:500, Santa Cruze Biotechnology) for 2 h, and stained with Alexa Fluor 488 anti-mouse secondary antibody (1:1000, Thermo Fisher Scientific) for 1 h at 4 °C. anti-HSV-1suggested: Noneanti-mousesuggested: (Thermo Fisher Scientific Cat# 88-7774-75, RRID:AB_476399)After washing 3 times with PBS, the cells were incubated with rabbit … SciScore for 10.1101/2020.11.14.382770: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The cells were then washed with PBS twice, blocked by 5% BSA and incubated with mouse anti-HSV-1 gD monoclonal antibody (1:500, Santa Cruze Biotechnology) for 2 h, and stained with Alexa Fluor 488 anti-mouse secondary antibody (1:1000, Thermo Fisher Scientific) for 1 h at 4 °C. anti-HSV-1suggested: Noneanti-mousesuggested: (Thermo Fisher Scientific Cat# 88-7774-75, RRID:AB_476399)After washing 3 times with PBS, the cells were incubated with rabbit anti-NXF1/TAP primary antibody (1:500, Cell Signaling Technology) and Alexa Fluor 594 anti-rabbit secondary antibody (1:500, Thermo Fisher Scientific), followed by staining the nucleus with DAPI. anti-NXF1/TAPsuggested: Noneanti-rabbitsuggested: NoneExperimental Models: Cell Lines Sentences Resources Cells, viruses, and compounds: African green monkey kidney epithelial cells (Vero, ATCC) and HEK293 T cells (ATCC) were cultured in DMEM containing 10% fetal bovine serum (FBS, Gibco Invitrogen) at 37 °C, 5% CO2. HEK293suggested: NoneThe fused proteins Aly/Ref-EGFP and NXF1/TAP-mCherry were transiently expressed in HEK293T cells by transfection with lipofectamine 2000. HEK293Tsuggested: NoneConfocal assay: Vero cells in confocal dishes were infected with HSV-1/Patton/GFP (MOI=0.2), and then treated with RDT at 1 μM. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Software and Algorithms Sentences Resources Statistical analyses were conducted using Prism, version 8.0. Prismsuggested: (PRISM, RRID:SCR_005375)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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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.
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