A Cell-based HTS to discover molecules that inhibit VEEV, encephalitic alphavirus - Project Summary - BioAssay Summary
This project seeks to discover small molecules active in inhibiting replication of Venezuelan Equine Encephalitis Viruses (VEEV), by utilizing a high throughput screening (HTS) campaign from the Molecular Library Program Center Network (MLPCN). VEEV, an encephalitic alphavirus, is listed as a select agent for its ability to cause severe disease during epidemics, as well as, its potential use a more ..
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AID: 588723
Data Source: Southern Research Specialized Biocontainment Screening Center (VEEV_Summary)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2011-10-30
Modify Date: 2012-12-16
Depositor Specified Assays
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AIDNameTypeComment
588727A Cell-Based Confirmatory Screen for Compounds that Inhibit VEEV, TC-83confirmatoryPrimary and Confirmatory Assays
602241A Cell-Based Confirmatory Screen for Compounds that Inhibit VEEV, TC-83 (2)confirmatoryConfirmatory (TC-83)
602455A Cell-Based Confirmatory Screen for Compounds that Inhibit VEEV, TC-83 (3)confirmatoryConfirmatory (TC-83)
624063A Cell-Based Confirmatory Screen for Compounds that Inhibit VEEV TC-83 (4)confirmatoryConfirmatory (TC-83)
624284A Cell-Based Confirmatory Screen for Compounds that Inhibit VEEV, TC-83 (5)confirmatoryConfirmatory (TC-83)
624449On Hold
651734On Hold
651917On Hold
602242A Cell-Based Counter Screen testing Compounds that Inhibit VEEV TC-83, in strain KU V3526confirmatoryCounter (v3586)
651884On Hold
602484A Cell-Based Confirmatory Screen for Compounds that Inhibit VEEV, Trinidad Donkey (TrD) (1)confirmatoryConfirmatory (Trinidad Donkey)
651874On Hold
588719Vero 76 Cytoxicity Assay for VEEV CompoundsconfirmatoryCytotoxicity counter screen (Vero 76)
602240Vero 76 Cytoxicity Assay for VEEV Compounds (2)confirmatoryCytotoxicity counter screen (Vero 76)
602439Vero 76 Cytoxicity Assay for VEEV Compounds (3)confirmatoryCytotoxicity counter screen (Vero 76)
624069Vero 76 Cytoxicity Assay for VEEV Compounds (5)confirmatoryCytotoxicity counter screen (Vero 76)
624295Vero 76 Cytoxicity Assay for VEEV Compounds (6)confirmatoryCytotoxicity counter screen (Vero 76)
624450On Hold
651735On Hold
651930On Hold
602307Virus Titer Reduction Secondary Screen for Compounds that Inhibit VEEV (TC-83 strain)otherVirus Titer Reduction (TC-83)
624286Virus Titer Reduction Secondary Screen for Compounds that Inhibit VEEV (TC-83 strain) (3)otherVirus Titer Reduction (TC-83)
651578On Hold
651886On Hold
602411Virus Titer Reduction Secondary Screen for Compounds that Inhibit VEEV (2) Trinidad donkey strainotherVirus Titer Reduction (Trinidad Donkey)
651883On Hold
602470A Counter Screen of Venezuelan Equine Encephalitis Virus (VEEV) Inhibitors in a Cell-Based Anti-Respiratory Syncytial Virus (RSV) AssayconfirmatoryRSV
651932On Hold
602483HEp2 Cytoxicity Assay for VEEV Compounds (1)confirmatoryCytotoxicity counter screen (Hep-2)
623935A Cell-Based Secondary Assay for Compounds that Inhibit VEEV, TC-83 and other Alphaviruses (Chikungunya virus)confirmatoryCHIKV
651738On Hold
651934On Hold
623936Vero 76 Cytoxicity Assay for VEEV Compounds (4)confirmatoryCytotoxicity counter screen (Vero 76)
Description:
Southern Research's Specialized Biocontainment Screening Center (SRSBSC)
Southern Research Institute (Birmingham, Alabama)
NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Assay Provider: Dong Hoon Chung, University of Louisville
Award: 1 R03 MH087448-01A1

This project seeks to discover small molecules active in inhibiting replication of Venezuelan Equine Encephalitis Viruses (VEEV), by utilizing a high throughput screening (HTS) campaign from the Molecular Library Program Center Network (MLPCN). VEEV, an encephalitic alphavirus, is listed as a select agent for its ability to cause severe disease during epidemics, as well as, its potential use a bioterrorism weapon. However, there is no FDA-approved treatment or prophylaxis of VEEV-related diseases at this time. Antiviral drug discovery for select agents has been impractical due to restrictions on handling the agents. Hence, successful outcomes from this project will benefit the public and the military.

According to the first specific aim for the project, the primary and confirmatory screening campaign utilized an attenuated VEEV strain, TC-83, that produced a robust cytopathic effect in Vero76 cells and narrowed the focus of the >300K MLSMR library to a subset of compounds. The attenuated strain has a significantly high homology between its genome sequence (99.9% homology with 11 mutations in 11,443 base pairs) and the wild type VEEV and therefore the probability for the hits evaluated in this assay would be active for wild type VEEV as well. The secondary assays described below address the requirements for specificity and selectivity as highlighted in specific aim 2 for this project and further delineate the compounds and scaffolds that will be further pursued through medicinal chemistry.
Additional Information
Grant Number: 1 R03 MH087448-01A1

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