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BioAssay: AID 720581

qHTS for Stage-Specific Inhibitors of Vaccinia Orthopoxvirus: Summary

Orthopoxviruses are a genus of viruses that include monkeypox, variola (the causative agent of smallpox) and vaccinia, the prototypical orthopoxvirus which was used in the world-wide vaccination program that eradicated smallpox [1]. Smallpox was once the most deadly human pathogen, and is estimated to have killed more than 300 million people. Following the eradication of smallpox, routine more ..
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 Related BioAssays
 Related BioAssays
AID: 720581
Data Source: NCGC (Vaccinia-summary)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2013-08-19
Modify Date: 2013-08-21
Target
Related Experiments
Show more
AIDNameTypeComment
720579qHTS for Stage-Specific Inhibitors of Vaccinia Orthopoxvirus: mCherry Reporter Primary qHTSConfirmatorydepositor-specified cross reference
720580qHTS for Stage-Specific Inhibitors of Vaccinia Orthopoxvirus: Venus Reporter Primary qHTSConfirmatorydepositor-specified cross reference
977615On Hold
977616On Hold
977617On Hold
1053115A549 24 hour CellTiterGlo cytotoxicity Measured in Cell-Based System Using Plate Reader - 2142-02_Inhibitor_Dose_CherryPick_ActivityConfirmatorydepositor-specified cross reference
1053133Assay for stage-specific inhibitors of Vaccinia orthopox Measured in Cell-Based and Microorganism Combination System Using Plate Reader - 2142-01_Inhibitor_SinglePoint_HTS_ActivityScreeningdepositor-specified cross reference
1053166On Hold
1053167On Hold
1053168On Hold
Description:
Orthopoxviruses are a genus of viruses that include monkeypox, variola (the causative agent of smallpox) and vaccinia, the prototypical orthopoxvirus which was used in the world-wide vaccination program that eradicated smallpox [1]. Smallpox was once the most deadly human pathogen, and is estimated to have killed more than 300 million people. Following the eradication of smallpox, routine vaccination was discontinued in the 1970s, and there has consequently been a precipitous decline in population immunity to smallpox and other orthopoxviruses. There are currently no FDA-licensed drugs to treat infected individuals, which is a significant concern given the threat of orthopoxvirus weaponization and the rise in reports of humans infected with monkeypox, which is endemic to Central and Western Africa [2]. Potent and validated inhibitors of this assay will be of significant interest to public and will provide the development of initial "hits" into therapeutic agents, either as a single agent or as a combination therapy with existing anti-viral agents.

In collaboration with the Connor lab, a quantitative high throughput assay using vaccinia virus model system was developed. The assay used recombinant viruses (coupled reporter system) that robustly monitor viral gene expression and viral spread to identify novel anti-orthopoxviral compounds. The first infection evaluates the stage gene expression in Vaccinia using the fluorescent Venus protein while the late infection uses the fluorescent mCherry protein reporter. Subsequent secondary and counterscreens will confirm true inhibitors that are not cytotoxic and elucidate the modes of action of confirmed inhibitors.

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

MLPCN Grant: MH094169
Assay Submitter (PI): John Connor, Boston University

[1] Moss B (2007) Poxviridae: The Viruses and Their Replication. In: Knipe DMH, P.M., editor. Fields Virology. 5 ed: Lippincott Williams & Wilkins.

[2] Rimoin AW, Kisalu N, Kebela-Ilunga B, Mukaba T, Wright LL et al. (2007) Endemic human monkeypox, Democratic Republic of Congo, 2001-2004. Emerg Infect Dis 13(6):934-937
Protocol
Please refer to the individual assays for detailed description of their corresponding protocol.
Comment
Assays will be linked as they become available.
Additional Information
Grant Number: MH094169

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