Tafenoquine inhibits replication of SARS-Cov-2 at pharmacologically relevant concentrations in vitro
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Abstract
Tafenoquine [TQ] exhibited EC50/90s of ~ 2.6/5.1 μM against SARS-CoV-2 in VERO E6 cells and was 4-fold more potent than hydroxychloroquine [HCQ]. Time-of-addition experiments were consistent with a different mechanism for TQ v HCQ. Physiologically based pharmacokinetic (PBPK) modeling suggested that lung unbound concentrations of TQ in COVID-19 patients may exceed the EC90 for at least 8 weeks after administration. The therapeutic potential for TQ in management of COVID-19 should be further evaluated.
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SciScore for 10.1101/2020.07.12.199059: (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. Table 2: Resources
No key resources detected.
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 …
SciScore for 10.1101/2020.07.12.199059: (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. Table 2: Resources
No key resources detected.
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.
- No funding statement was detected.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.07.12.199059: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19. N Engl J Med. 2020 Jun 3:NEJMoa2016638. doi: 10.1056. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Briefly, SARSCoV-2-infected VERO E6 cell monolayers [at multiplicity of infection [moi] of 0.05] in 96-well plates were incubated at 37°C in 5% CO2 while exposed to differing concentrations of TQ, remdesivir [RD] and HCQ in triplicate wells in minimum essential medium supplemented with 1% (w/v) … SciScore for 10.1101/2020.07.12.199059: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19. N Engl J Med. 2020 Jun 3:NEJMoa2016638. doi: 10.1056. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Briefly, SARSCoV-2-infected VERO E6 cell monolayers [at multiplicity of infection [moi] of 0.05] in 96-well plates were incubated at 37°C in 5% CO2 while exposed to differing concentrations of TQ, remdesivir [RD] and HCQ in triplicate wells in minimum essential medium supplemented with 1% (w/v) L-glutamine, 2% fetal bovine serum and 0.2% DMSO [the latter for compound dissolution]. VERO E6suggested: NoneSoftware and Algorithms Sentences Resources Whole lung, lung-unbound, and plasma concentrations at an assumed lung pH of 6 were simulated using Simcyp [V19.1, Simcyp Ltd, Sheffield, UK] as described by Rowland Yeo et al, [18]. Simcypsuggested: (Simcyp, SCR_003944)EMBO J 11:2695-700. EMBO Jsuggested: NoneAbout 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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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