Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, A Potential Oral Drug Candidate for COVID-19 Treatment

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   ScreenIT

   Feb 10, 2022

   SciScore for 10.1101/2022.02.07.478848: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	Field Sample Permit: In-life dog and monkey PK studies were conducted at Absorption System (San Diego, CA) and Frontage Labs (Concord, OH), respectively. IACUC: All experimental procedures were reviewed and approved by the Animal Care and Use Committee (ACUC) of the NIH Division of Veterinary Resources (DVR) or CRO labs for in-life studies.
   Sex as a biological variable	Control male C57BL6 mouse, Sprague Dawley rat, Cynomolgus monkey and Beagle dog plasmas were ordered from Bioreclamation IVT (Westbury, NY, U.S.A.).
   Randomization	not detected.
   Blinding	not detected.
   Power Analysis	not detected.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Experimental Models: Cell Lines
   Sentences	Resources
   The …

   SciScore for 10.1101/2022.02.07.478848: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	Field Sample Permit: In-life dog and monkey PK studies were conducted at Absorption System (San Diego, CA) and Frontage Labs (Concord, OH), respectively. IACUC: All experimental procedures were reviewed and approved by the Animal Care and Use Committee (ACUC) of the NIH Division of Veterinary Resources (DVR) or CRO labs for in-life studies.
   Sex as a biological variable	Control male C57BL6 mouse, Sprague Dawley rat, Cynomolgus monkey and Beagle dog plasmas were ordered from Bioreclamation IVT (Westbury, NY, U.S.A.).
   Randomization	not detected.
   Blinding	not detected.
   Power Analysis	not detected.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Experimental Models: Cell Lines
   Sentences	Resources
   The apical layer supernatant samples were diluted at 1 to 8 ratio that were added to 96-well assay plates containing 10,000/well Vero E6 cells, followed by incubation at 37°C, 5% CO2 and 95% relative humidity.	Vero E6 suggested: RRID:CVCL_XD71)
   Transporter assays: MDR1 and BCRP substrate screening: Caco-2 (American Type Culture Collection), MDR1-MDCK (NIH), and BCRP-MDCK (transfected by Absorption Systems) cell monolayers were grown to confluence on collagen-coated, microporous membranes in 12-well assay plates.	Caco-2 suggested: None MDR1-MDCK suggested: None
   Caco-2 cells were cultured for 27 days, MDCK-MDR1 and MDCK-BCRP cells were cultured for 8 days prior to experiments.	MDCK-MDR1 suggested: RRID:CVCL_S586) MDCK-BCRP suggested: None
   Nucleoside transporters: MDCK-II cells were maintained in DMEM with low glucose and 10% FBS.	MDCK-II suggested: None
   Experimental Models: Organisms/Strains
   Sentences	Resources
   Cryopreserved mixed-gender human, male Sprague-Dawley rat, male CD-1 mouse, male Beagle dog, and male Cynomolgus monkey hepatocytes (Sekisui XenoTech, LLC) were thawed and equilibrated at 37°C.	Sprague-Dawley suggested: None CD-1 suggested: None
   The net transporter-mediated uptake rate of the substrate by each transporter was calculated: Percent inhibition was calculated by dividing the transporter-mediated uptake rate in presence of the test article or the reference inhibitor by the transporter-mediated uptake rate in presence of vehicle control: Pharmacokinetics studies: Adult male C57BL/6 mice and Sprague Dawley rats were purchased from Charles River Laboratory (Wilmington, MA).	C57BL/6 suggested: None Sprague Dawley suggested: RRID:RGD_737903)
   Male C57BL6 mice (n = 3 per time point, 24 - 40 g) were dosed at 5 mg/kg IV or 10 mg/kg oral gavage.	C57BL6 suggested: None
   Male Sprague–Dawley rats (n = 3 or 4 per treatment group, ∼ 343–375 g) were dosed in IV and PO dosing groups: 1 and 5 mg/kg IV, and 10, 30 and 100 mg/kg PO, respectively.	Sprague–Dawley suggested: None
   Software and Algorithms
   Sentences	Resources
   Pharmacokinetics analysis: Phoenix WinNonlin, version 8.1 (Certara, St. Louis, MO), was used to perform PK analysis with the non-compartmental approach (Models 200 and 201 for PO and IV datasets).	Phoenix WinNonlin suggested: None

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   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).

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   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.

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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   Results from JetFighter: We did not find any issues relating to colormaps.

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

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   Version published to 10.1101/2022.02.07.478848v1 on bioRxiv

   Feb 7, 2022