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BioAssay: AID 540276

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(284168)
 
 
Active(4700)
 
 
Inactive(201162)
 
 
Inconclusive(80053)
 
 
 Tested Substances
 Tested Substances
All(301745)
 
 
Active(5375)
 
 
Inactive(212052)
 
 
Inconclusive(84318)
 
 
AID: 540276
Data Source: NCGC (VSVM001)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2011-07-20
Modify Date: 2011-11-18

Data Table ( Complete ):           Active    All
Target
BioActive Compounds: 4700
Depositor Specified Assays
AIDNameTypeComment
463114qHTS screen for inhibitors of Lassa infection: SummarysummaryVSV-L summary AID
540249Inhibitors of binding or entry into cells for Lassa Virus: Summarysummary
540278Summary of inhibitors of binding or entry into cells for Marburg Virussummary
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
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 inhibitors, the 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.
Result Definitions
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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
5Curve_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
6Fit_LogAC50The logarithm of the AC50 from a fit of the data to the Hill equation (calculated based on Molar Units).Float
7Fit_HillSlopeThe Hill slope from a fit of the data to the Hill equation.Float
8Fit_R2R^2 fit value of the curve. Closer to 1.0 equates to better Hill equation fit.Float
9Fit_InfiniteActivityNumerical encoding of curve description for the fitted Hill equation.Float
10Fit_ZeroActivityEfficacy at zero concentration of compound from a fit of the data to the Hill equation.Float%
11Fit_CurveClassNumerical encoding of curve description for the fitted Hill equation.Float
12Excluded_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
13Max_ResponseMaximum activity observed for compound (usually at highest concentration tested).Float%
14Activity at 0.0003896194 uM (0.000389619μM**)% Activity at given concentration.Float%
15Activity at 0.0008864618 uM (0.000886462μM**)% Activity at given concentration.Float%
16Activity at 0.00266 uM (0.00266μM**)% Activity at given concentration.Float%
17Activity at 0.00700 uM (0.007μM**)% Activity at given concentration.Float%
18Activity at 0.011 uM (0.011μM**)% Activity at given concentration.Float%
19Activity at 0.024 uM (0.024μM**)% Activity at given concentration.Float%
20Activity at 0.072 uM (0.072μM**)% Activity at given concentration.Float%
21Activity at 0.190 uM (0.19μM**)% Activity at given concentration.Float%
22Activity at 0.449 uM (0.449μM**)% Activity at given concentration.Float%
23Activity at 1.923 uM (1.923μM**)% Activity at given concentration.Float%
24Activity at 5.798 uM (5.798μM**)% Activity at given concentration.Float%
25Activity at 14.25 uM (14.25μM**)% Activity at given concentration.Float%
26Activity at 37.76 uM (37.76μM**)% Activity at given concentration.Float%
27Activity at 46.10 uM (46.1μM**)% Activity at given concentration.Float%
28Compound QCSource of compoundString

* Activity Concentration. ** Test Concentration.
Additional Information
Grant Number: MH086850

Data Table (Concise)
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