Ethacridine inhibits SARS-CoV-2 by inactivating viral particles
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Abstract
The respiratory disease COVID-19 is caused by the coronavirus SARS-CoV-2. Here we report the discovery of ethacridine as a potent drug against SARS-CoV-2 (EC 50 ~ 0.08 μ M). Ethacridine was identified via high-throughput screening of an FDA-approved drug library in living cells using a fluorescence assay. Plaque assays, RT-PCR and immunofluorescence imaging at various stages of viral infection demonstrate that the main mode of action of ethacridine is through inactivation of viral particles, preventing their binding to the host cells. Consistently, ethacridine is effective in various cell types, including primary human nasal epithelial cells that are cultured in an air-liquid interface. Taken together, our work identifies a promising, potent, and new use of the old drug via a distinct mode of action for inhibiting SARS-CoV-2.
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SciScore for 10.1101/2020.10.28.359042: (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 Immunostaining was further carried out using an antibody against nucleocapsid (Genetex, SARS-CoV-2 (COVID-19 antibody against nucleocapsid ( Genetex , SARS-CoV-2suggested: None9) nucleocapsid antibody, GTX135357) or an antibody against spike (Genetex, SARS-CoV-2 (COVID-19) spike antibody [1A9], GTX632604) and visualized with goat anti-rabbit IgG H&L (Alexa Fluor® 488) (Abcam, ab150077) or goat anti-mouse IgG H&L (Alexa Fluor® 555) (Abcam, ab150114). GTX135357SciScore for 10.1101/2020.10.28.359042: (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 Immunostaining was further carried out using an antibody against nucleocapsid (Genetex, SARS-CoV-2 (COVID-19 antibody against nucleocapsid ( Genetex , SARS-CoV-2suggested: None9) nucleocapsid antibody, GTX135357) or an antibody against spike (Genetex, SARS-CoV-2 (COVID-19) spike antibody [1A9], GTX632604) and visualized with goat anti-rabbit IgG H&L (Alexa Fluor® 488) (Abcam, ab150077) or goat anti-mouse IgG H&L (Alexa Fluor® 555) (Abcam, ab150114). GTX135357suggested: (GeneTex Cat# GTX135357, RRID:AB_2868464)GTX632604suggested: (GeneTex Cat# GTX632604, RRID:AB_2864418)anti-rabbit IgGsuggested: (Abcam Cat# ab150077, RRID:AB_2630356)anti-mouse IgGsuggested: (Abcam Cat# ab150114, RRID:AB_2687594)Experimental Models: Cell Lines Sentences Resources To check the FlipGFPMpro signal after SARS-CoV-2 infection, HEK293T on 10-mm coverglasses were transfected with 200 ng of pcDNA3.1-hACE2 (Addgene, #145033) 24 hours later. HEK293Tsuggested: NoneThose 293T cells were further infected with SARS-CoV-2 at an MOI of 0.5. 293Tsuggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)A clinical isolate of SARS-CoV-2 (USA-WA1/2020, BEI Cat No: NR-52281) was propagated in Vero E6 cells. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources Images were acquired using Nikon Eclipse Ti-E Spinning Disk under 60X and processed in ImageJ. ImageJsuggested: (ImageJ, RRID:SCR_003070)Statistics: All statistics were performed in GraphPad Prism. GraphPad Prismsuggested: (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 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: Please consider improving the rainbow (“jet”) colormap(s) used on page 12. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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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