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BioAssay: AID 540256

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

Lassa virus is an arenavirus that is endemic in West Africa and can cause severe hemorrhagic fever in humans. Lassa virus is composed of a nucleocapsid core surrounded by a lipid bilayer containing glycoproteins that mediate host cell binding. To identify inhibitors of Lassa virus entry into cells, a pseudotype virus system was used where the nonpathogenic vesicular stomatitis virus (VSV) more ..
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 Tested Compounds
 Tested Compounds
All(297149)
 
 
Active(3648)
 
 
Inactive(235534)
 
 
Inconclusive(58801)
 
 
 Tested Substances
 Tested Substances
All(300904)
 
 
Active(3699)
 
 
Inactive(237813)
 
 
Inconclusive(59392)
 
 
 Related BioAssays
 Related BioAssays
AID: 540256
Data Source: NCGC (VSVL001)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2011-07-15
Modify Date: 2011-07-23

Data Table ( Complete ):           Active    All
BioActive Compounds: 3648
Depositor Specified Assays
AIDNameTypeComment
463114qHTS screen for inhibitors of Lassa infection: Summarysummary
540249Inhibitors of binding or entry into cells for Lassa Virus: Summarysummary
Description:
Lassa virus is an arenavirus that is endemic in West Africa and can cause severe hemorrhagic fever in humans. Lassa virus is composed of a nucleocapsid core surrounded by a lipid bilayer containing glycoproteins that mediate host cell binding. To identify inhibitors of Lassa virus entry into cells, a pseudotype virus system was used where the nonpathogenic vesicular stomatitis virus (VSV) contains the Lassa virus envelop glycoproteins. This pseudotype virus, termed VSV-LV, has a Photinus luciferase reporter gene inserted in its genome. For this assay, human embryonic kidney 293 cells are incubated with VSV-LV and virus entry is detected by luminescence produced from the luciferase reporter. Small molecule inhibitors that block VSV-LV 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 miniaturized, 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
For screening, 1000 cells in 2 ul/well were dispensed into white solid 1536-well plates (Greiner) using a solenoid-based dispenser. Following transfer of 23nl compound or DMSO vehicle by a pin tool, 3 ul/well of VSV-LV was added. The plates were centrifuged 1 min at 1000 RPM and then incubated 16 hr at 37 C and 5% CO2. After addition of 4 ul/well SteadyLite (PerkinElmer) detection reagent, the plates were incubated 10 min at ambient temperature and luminescence was measured on a ViewLux (Perkin Elmer) plate reader.

Keywords: NIH Roadmap, MLPCN, MLI, MLSMR, qHTS, NCGC, Lassa virus, luciferase, cell assay, infection
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.
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_InfiniteActivityThe asymptotic efficacy from a fit of the data to the 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 0.00266 uM (0.00266μM**)% Activity at given concentration.Float%
15Activity at 0.072 uM (0.072μM**)% Activity at given concentration.Float%
16Activity at 0.190 uM (0.19μM**)% Activity at given concentration.Float%
17Activity at 0.450 uM (0.45μM**)% Activity at given concentration.Float%
18Activity at 0.853 uM (0.853μM**)% Activity at given concentration.Float%
19Activity at 1.923 uM (1.923μM**)% Activity at given concentration.Float%
20Activity at 5.798 uM (5.798μM**)% Activity at given concentration.Float%
21Activity at 14.28 uM (14.28μM**)% Activity at given concentration.Float%
22Activity at 37.87 uM (37.87μM**)% Activity at given concentration.Float%
23Activity at 46.10 uM (46.1μM**)% Activity at given concentration.Float%
24Compound QCNCGC designation for data stage: 'qHTS', 'qHTS Verification', 'Secondary Profiling'String

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

Data Table (Concise)
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