Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 In Vitro
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Abstract
Antivirals targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could improve treatment of COVID-19. We evaluated the efficacy of clinically relevant hepatitis C virus (HCV) NS3 protease inhibitors (PIs) against SARS-CoV-2 and their interactions with remdesivir, the only direct-acting antiviral approved for COVID-19 treatment.
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SciScore for 10.1101/2020.12.02.408112: (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 Then plates were washed 2 times with PBS-tween and incubated for 1 hour at room temperature with secondary antibody F(ab’)2-Goat anti-human IgG Fc Cross-Adsorbed Secondary Antibody, HRP (Invitrogen#A24476, Carlsbad, CA, USA) or Goat F(ab’)2 Anti-Human IgG – Fc (HRP), preadsorbed (Abcamab#98595, Cambridge, UK), diluted 1:2,000 in PBSK. anti-human IgGsuggested: (Thermo Fisher Scientific Cat# A24476, RRID:AB_2535945)Experimental Models: Cell Lines Sentences Reso… SciScore for 10.1101/2020.12.02.408112: (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 Then plates were washed 2 times with PBS-tween and incubated for 1 hour at room temperature with secondary antibody F(ab’)2-Goat anti-human IgG Fc Cross-Adsorbed Secondary Antibody, HRP (Invitrogen#A24476, Carlsbad, CA, USA) or Goat F(ab’)2 Anti-Human IgG – Fc (HRP), preadsorbed (Abcamab#98595, Cambridge, UK), diluted 1:2,000 in PBSK. anti-human IgGsuggested: (Thermo Fisher Scientific Cat# A24476, RRID:AB_2535945)Experimental Models: Cell Lines Sentences Resources Cell cultivation: African green monkey kidney VeroE6 cells (gift from J. Dubuisson) and human hepatoma Huh7.5 cells83 were maintained at 37°C and 5% CO2 in Dulbecco’s Modified Eagle Medium (Invitrogen, Paisley, UK) supplemented with 10% heat inactivated fetal bovine serum (Sigma, Saint Louis Missouri, USA) and 100 U/mL penicillin with 100μL streptomycin (Gibco/Invitrogen corporation, Carlsbad, California, USA). Huh7.5suggested: RRID:CVCL_YU20)In brief, VeroE6 cells were seeded at 10,000 cells per well in 96-well flat-bottom plates, medium was changed to 50 μL fresh medium, and cells were inoculated with SARS-CoV-2/human/Denmark/DK-AHH1/2020 at MOI 0.0016 by adding 50 μL virus stock diluted in medium to each well. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Software and Algorithms Sentences Resources Cell cultivation: African green monkey kidney VeroE6 cells (gift from J. Dubuisson) and human hepatoma Huh7.5 cells83 were maintained at 37°C and 5% CO2 in Dulbecco’s Modified Eagle Medium (Invitrogen, Paisley, UK) supplemented with 10% heat inactivated fetal bovine serum (Sigma, Saint Louis Missouri, USA) and 100 U/mL penicillin with 100μL streptomycin (Gibco/Invitrogen corporation, Carlsbad, California, USA). Gibco/Invitrogensuggested: NoneSigmoidal concentration response curves were fitted and EC50 values calculated as described previously using Graphpad Prism 8.0.0 with a bottom constraint of 0 applying the formula Y= Top/(1+10(Log10EC50-X)*HillSlope). Graphpad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)The images were acquired with ZEN 3.0 software. ZENsuggested: NoneResults 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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 40, 38 and 39. 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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