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BioAssay: AID 720532

qHTS for Inhibitors of binding or entry into cells for Marburg Virus

Marburg virus is a filovirus that is originated in Central and East Africa and can cause Marburg hemorrhagic fever in humans. Marburg virus is in the same taxonomic family as Ebola virus. Marburg virus is enveloped, nonsegmented, and contains a negative-sense RNA strand. To identify inhibitors of Marburg virus entry into cells, a pseudotype virus system was used where the nonpathogenic vesicular more ..
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 Tested Compounds
 Tested Compounds
All(15472)
 
 
Active(1039)
 
 
Inactive(11998)
 
 
Inconclusive(2848)
 
 
 Tested Substances
 Tested Substances
All(18110)
 
 
Active(1181)
 
 
Inactive(13902)
 
 
Inconclusive(3027)
 
 
AID: 720532
Data Source: NCGC (VSVM-OFFLINE)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2013-07-20

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 1039
Related Experiments
AIDNameTypeComment
540278Summary of inhibitors of binding or entry into cells for Marburg VirusSummarydepositor-specified cross reference
463114qHTS screen for inhibitors of Lassa infection: SummarySummarysame project related to Summary assay
540276qHTS for inhibitors of binding or entry into cells for Marburg VirusConfirmatorysame project related to Summary assay
Description:
Marburg virus is a filovirus that is originated in Central and East Africa and can cause Marburg hemorrhagic fever in humans. Marburg virus is in the same taxonomic family as Ebola virus. Marburg virus is enveloped, nonsegmented, and contains a negative-sense RNA strand. To identify inhibitors of Marburg virus entry into cells, a pseudotype virus system was used where the nonpathogenic vesicular stomatitis virus (VSV) contains the Marburg virus envelop glycoproteins. This pseudotype virus, termed VSV-MARV, has a Photinus luciferase reporter gene inserted in its genome. For this assay, human embryonic kidney 293 cells are incubated with VSV-MARV and virus entry is detected by luminescence produced from the luciferase reporter. Small molecule inhibitors that block VSV-MARV binding or entry into cells are identified by a decrease of luciferase activity.

In a collaboration between University of Texas Medical Branch in Galveston, TX and the NIH Chemical Genomics Center (NCGC) a miniturized, high throughput, cell-based assay was developed and screened against the Molecular Libraries Small Molecule Repository (MLSMR) library.

NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Centers Network [MLPCN]

MLPCN Grant: MH086850-01A1
Assay Submitter (PI): Robert Davey, University of Texas Medical Branch, Galveston, TX
Protocol
Two uL of HEK293 cell suspension are dispensed at 1000 cells/well into solid white 1536-well plates (Grenier) using a Multidrop Combi (Thermo Scientific). After addition of 23 nL compound by a pin tool (Kalypsys), the plate is incubated 1 h at 37 degrees C and then 3 uL of virus 1:100 dilution VSV-MARV is added. After 28 hr, 4 uL of assay reagent is added and the plates are read using a ViewLux (Perkin Elmer). Assays are performed in sub-saturating amounts of virus (MOI <0.5), therefore luciferase signals reflect the amount (titer) of virus able to infect the cells in presence of the compound.
Comment
Compound Ranking:
1. Compounds are first classified as having full titration curves, partial modulation, partial curve (weaker actives), single point activity (at highest concentration only), or inactive. See data field "Curve Description". For this assay, apparent inhibitors are ranked higher than compounds that showed apparent activation.
2. For all inactive compounds, PUBCHEM_ACTIVITY_SCORE is 0. For all active compounds, a score range was given for each curve class type given above. Active compounds have PUBCHEM_ACTIVITY_SCORE between 40 and 100. Inconclusive compounds have PUBCHEM_ACTIVITY_SCORE between 1 and 39. Fit_LogAC50 was used for determining relative score and was scaled to each curve class' score range.
Categorized Comment - additional comments and annotations
From PubChem:
Assay Cell Type: HEK293
Result Definitions
Show more
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1PhenotypeIndicates type of activity observed: inhibitor, activator, fluorescent, cytotoxic, inactive, or inconclusive.String
2Potency*Concentration at which compound exhibits half-maximal efficacy, AC50. Extrapolated AC50s also include the highest efficacy observed and the concentration of compound at which it was observed.FloatμM
3EfficacyMaximal efficacy of compound, reported as a percentage of control. These values are estimated based on fits of the Hill equation to the dose-response curves.Float%
4Analysis CommentAnnotation/notes on a particular compound's data or its analysis.String
5Activity_ScoreActivity score.Integer
6Curve_DescriptionA description of dose-response curve quality. A complete curve has two observed asymptotes; a partial curve may not have attained its second asymptote at the highest concentration tested. High efficacy curves exhibit efficacy greater than 80% of control. Partial efficacies are statistically significant, but below 80% of control.String
7Fit_LogAC50The logarithm of the AC50 from a fit of the data to the Hill equation (calculated based on Molar Units).Float
8Fit_HillSlopeThe Hill slope from a fit of the data to the Hill equation.Float
9Fit_R2R^2 fit value of the curve. Closer to 1.0 equates to better Hill equation fit.Float
10Fit_InfiniteActivityThe asymptotic efficacy from a fit of the data to the Hill equation.Float%
11Fit_ZeroActivityEfficacy at zero concentration of compound from a fit of the data to the Hill equation.Float%
12Fit_CurveClassNumerical encoding of curve description for the fitted Hill equation.Float
13Excluded_PointsWhich dose-response titration points were excluded from analysis based on outlier analysis. Each number represents whether a titration point was (1) or was not (0) excluded, for the titration series going from smallest to highest compound concentrations.String
14Max_ResponseMaximum activity observed for compound (usually at highest concentration tested).Float%
15Activity at 0.0000000311 uM (3.10866e-08μM**)% Activity at given concentration.Float%
16Activity at 0.0000000880 uM (8.80184e-08μM**)% Activity at given concentration.Float%
17Activity at 0.0000001756 uM (1.75576e-07μM**)% Activity at given concentration.Float%
18Activity at 0.0000004972 uM (4.97236e-07μM**)% Activity at given concentration.Float%
19Activity at 0.0000014063 uM (1.40634e-06μM**)% Activity at given concentration.Float%
20Activity at 0.0000028127 uM (2.81268e-06μM**)% Activity at given concentration.Float%
21Activity at 0.0000079555 uM (7.95546e-06μM**)% Activity at given concentration.Float%
22Activity at 0.0000225014 uM (2.25014e-05μM**)% Activity at given concentration.Float%
23Activity at 0.0000450029 uM (4.50029e-05μM**)% Activity at given concentration.Float%
24Activity at 0.0001299230 uM (0.000129923μM**)% Activity at given concentration.Float%
25Activity at 0.0003002708 uM (0.000300271μM**)% Activity at given concentration.Float%
26Activity at 0.0008965874 uM (0.000896587μM**)% Activity at given concentration.Float%
27Activity at 0.00268 uM (0.00268115μM**)% Activity at given concentration.Float%
28Activity at 0.00700 uM (0.00700018μM**)% Activity at given concentration.Float%
29Activity at 0.016 uM (0.0164739μM**)% Activity at given concentration.Float%
30Activity at 0.032 uM (0.0316665μM**)% Activity at given concentration.Float%
31Activity at 0.076 uM (0.0761191μM**)% Activity at given concentration.Float%
32Activity at 0.219 uM (0.218613μM**)% Activity at given concentration.Float%
33Activity at 0.631 uM (0.63071μM**)% Activity at given concentration.Float%
34Activity at 1.728 uM (1.72828μM**)% Activity at given concentration.Float%
35Activity at 3.886 uM (3.88644μM**)% Activity at given concentration.Float%
36Activity at 8.589 uM (8.58887μM**)% Activity at given concentration.Float%
37Activity at 17.80 uM (17.7982μM**)% Activity at given concentration.Float%
38Activity at 49.20 uM (49.2015μM**)% Activity at given concentration.Float%
39Activity at 107.3 uM (107.251μM**)% Activity at given concentration.Float%
40Activity at 231.0 uM (231μM**)% Activity at given concentration.Float%
41Compound QCNCGC designation for data stage: 'qHTS', 'qHTS Verification', 'Secondary Profiling'String

* Activity Concentration. ** Test Concentration.
Additional Information
Grant Number: MH086850-01A1

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
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