Screening a Library of FDA-Approved and Bioactive Compounds for Antiviral Activity against SARS-CoV-2

Article activity feed

1. Version published to 10.1021/acsinfecdis.1c00017

   Jun 15, 2021
2. 

   ScreenIT

   Dec 31, 2020

   SciScore for 10.1101/2020.12.30.424862: (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

   Experimental Models: Cell Lines
   Sentences	Resources
   Huh-7 and HPMEC cells were obtained from Dr. Eva Harris (UC Berkeley) and maintained in D10 media or endothelial growth medium 2 (EGM-2) using the EGM-2 bullet kit from Lonza, respectively.	Huh-7 suggested: None
   LNCaP, HaCaT, Caco-2, Calu-3, HCT-116, and A549 cells were obtained from the UC Berkeley Cell Culture Facility and maintained in D10 media.	HaCaT suggested: None Caco-2 suggested: None Calu-3 suggested: None HCT-116 suggested: None A549 sug…

   SciScore for 10.1101/2020.12.30.424862: (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

   Experimental Models: Cell Lines
   Sentences	Resources
   Huh-7 and HPMEC cells were obtained from Dr. Eva Harris (UC Berkeley) and maintained in D10 media or endothelial growth medium 2 (EGM-2) using the EGM-2 bullet kit from Lonza, respectively.	Huh-7 suggested: None
   LNCaP, HaCaT, Caco-2, Calu-3, HCT-116, and A549 cells were obtained from the UC Berkeley Cell Culture Facility and maintained in D10 media.	HaCaT suggested: None Caco-2 suggested: None Calu-3 suggested: None HCT-116 suggested: None A549 suggested: None
   NCI-H1437 and RD cells were obtained from the Cell and Genome Engineering Core at UCSF via Dr. Olga Gulyaeva (UCSF) and Dr. Michael T. McManus (UCSF) and maintained in D10 media.	NCI-H1437 suggested: NCI-DTP Cat# NCI-H1437, RRID:CVCL_1472) RD suggested: None
   HBEC-30KT and BEAS-2B cells were obtained from Dr. Neil Tay (UCSF) and Dr. Michael T. McManus (UCSF) via Dr. Patrick Mitchell (UC Berkeley) and Dr. Russell Vance (UC Berkeley) and maintained in defined keratinocyte serum free medium (catalog #10744019, ThermoFisher Scientific) and Advanced RPMI containing 5% FBS, 1% L-glutamine, 1X PenStrep, respectively.	BEAS-2B suggested: None
   Huh-7.5.1 cells were obtained from Dr. Andreas Puschnik (Chan Zuckerberg Biohub) and maintained in D10 media.	Huh-7.5.1 suggested: RRID:CVCL_E049)
   HPMEC/hACE2 and A549/hACE2 cell lines were produced by transducing parental cells with lentivirus encoding the human ACE2 gene followed by puromycin selection (2 μg/ml) for three passages.	A549/hACE2 suggested: None
   The initial stock from BEI was passed through a 0.45 μM syringe filter and 5 μl of this filtered stock was inoculated onto ~80% confluent T175 flasks (Nunc, Roskilde, Denmark) of Vero-E6 cells to produce passage 1 of the virus.	Vero-E6 suggested: None
   Recombinant DNA
   Sentences	Resources
   The hACE2 encoding plasmid was a gift from Hyeryun Choe (Addgene plasmid # 1786; htt://n2t.net/addgene:1786; RRID:Addgene_1786) (54).	detected: RRID:Addgene_1786)
   Software and Algorithms
   Sentences	Resources
   The data was plotted and analyzed with Spotfire (Tibco) and GraphPad Prism (San Diego, CA).	GraphPad suggested: (GraphPad Prism, RRID:SCR_002798)
   In brief, candidate compounds identified in our screens were assigned distinct properties based on known host targets and pathways using the Center for Emerging and Neglected Diseases’ database and for pharmacokinetic data and transporter inhibition data, the DrugBank database.	DrugBank suggested: (DrugBank, RRID:SCR_002700)
   An average of 1×103 cells were imaged across four sites per well and were analyzed for nucleocapsid (N) stain per nuclei (DAPI) using CellProfiler 3.1.9 (Broad Institute, Cambridge, MA).	CellProfiler suggested: None
   Custom code written in MATLAB (available at https://gitlab.com/tjian-darzacq-lab/second-derivative-cq-analysis) was used to take the numerical second derivative of fluorescence intensity with respect to cycle number, using a sliding window of ± 3 cycles.	MATLAB suggested: (MATLAB, RRID:SCR_001622)

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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: We detected the following sentences addressing limitations in the study:

   Defining the mechanisms of action of antiviral compounds is critical to determine how a compound may be modified to improve antiviral efficacy and to suggest the compounds’ pharmacokinetic and pharmacodynamic limitations. An advantage of screening libraries of well characterized compounds is that the molecular targets of many compounds are already determined. GSEA analysis of our top antiviral candidates revealed a set of enriched host and viral targets. Our candidate compounds possess distinct mechanisms of action including host kinase and protease inhibition, anti-inflammatory activity, and direct antiviral efficacy targeting virus factors. Our results also implicate host-pathways that are critical for SARS-CoV-2 viral replication including regulation of the cell cycle through modulating CDKs, regulating MAPK signaling through modulation of c-JUN N-terminal kinases (JNK), and modulation of glycogen synthase kinase 3 (GSK-3). Our screening results are consistent with other reports that these diverse cellular pathways are likely to be critical for the SARS-CoV-2 lifecycle (21, 43–46). These observations call for further mechanistic investigation of the dependency of SARS-CoV-2 on these various host pathways and highlight the potential of repurposing other drugs not studied here that target these pathways. Though our study identified many distinct antiviral candidates, only dinaciclib exceeded the in vitro potency of remdesivir, suggesting that few, if any, “magic bullet” comp...

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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.
   • Thank you for including a protocol registration statement.

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3. 

   Version published to 10.1101/2020.12.30.424862v1 on bioRxiv

   Dec 30, 2020