| 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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Depositor Specified Assays
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 PageFrom: |
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