The Screening Core (SC) is a key component of the Antiviral Drug Discovery and Development Center, contributing to the goals of each ofthe individual projects. Through prior NIH funded programs the SC has a legacy set of hits from chemically diverse compound libraries that have not proceeded beyond the screening stage for each Research Team to asses immediately for their mechanism of action. Secondly, the SC will conduct high throughput screening campaigns of -160,000 never before screened compounds for each research project to provide novel hits as reasonable starting points for the Research Teams and Medicinal Chemistry and Lead development Core (MCLDC). These hits will be analyzed to define their mechanism of action by the Research Teams. Replication inhibitors from either the current or previous screening efforts will funnel into a MCLDC chemistry program designed to optimize their efficacy and selectivity. The SC will also assist the Research Teams and the MCLDC by providing screening data to support the structure activity relationship (SAR) projects to further the CETR's goal of developing new replication inhibitor therapeutics for the treatment of emerging pathogens. Having a core with medium throughput capacity is essential to meet the goal of having leads with the appropriate characteristics to enter animal studies within five years. The resulting data about these compounds, generated by the SC and Research Projects, will be maintained in a centralized database with easy access by the members of the project teams. The SC will incorporate key members ofthe MCLDC and Research Project teams into the screening and decision making procedures. The end result of this process will be the identification of novel compounds appropriate for IND enabling studies.
To combat novel emerging infections, drug resistant organisms, and potential weaponized biological threats, the identification of new therapeutic targets, and the development of drugs exploiting those targets, is essential. The overarching goal of this Core is to discover new chemical hits using high throughput screens for the new therapeutic targets identified by the Research Projects and to assist the MCLDC in converting them into drugs by providing biological screening support to the Project Teams.
|Mounce, Bryan C; Cesaro, Teresa; Moratorio, Gonzalo et al. (2016) Inhibition of Polyamine Biosynthesis Is a Broad-Spectrum Strategy against RNA Viruses. J Virol 90:9683-9692|
|Morrison, Clayton R; Plante, Kenneth S; Heise, Mark T (2016) Chikungunya Virus: Current Perspectives on a Reemerging Virus. Microbiol Spectr 4:|
|McCarthy, Mary K; Morrison, Thomas E (2016) Chronic chikungunya virus musculoskeletal disease: what are the underlying mechanisms? Future Microbiol 11:331-4|
|Rasmussen, Lynn; White, E Lucile; Bostwick, James R (2016) Acoustic Droplet Ejection Applications for High-Throughput Screening of Infectious Agents. J Lab Autom 21:188-97|
|Everts, Maaike; Suto, Mark J; Painter, George R et al. (2016) Consortia's critical role in developing medical countermeasures for re-emerging viral infections: a USA perspective. Future Virol 11:187-195|
|Haese, Nicole N; Broeckel, Rebecca M; Hawman, David W et al. (2016) Animal Models of Chikungunya Virus Infection and Disease. J Infect Dis 214:S482-S487|
|Broeckel, Rebecca; Haese, Nicole; Messaoudi, Ilhem et al. (2015) Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model). Pathogens 4:662-81|
|Chiang, Cindy; Beljanski, Vladimir; Yin, Kevin et al. (2015) Sequence-Specific Modifications Enhance the Broad-Spectrum Antiviral Response Activated by RIG-I Agonists. J Virol 89:8011-25|
|Sali, Tina M; Pryke, Kara M; Abraham, Jinu et al. (2015) Characterization of a Novel Human-Specific STING Agonist that Elicits Antiviral Activity Against Emerging Alphaviruses. PLoS Pathog 11:e1005324|
|Mainou, Bernardo A; Ashbrook, Alison W; Smith, Everett Clinton et al. (2015) Serotonin Receptor Agonist 5-Nonyloxytryptamine Alters the Kinetics of Reovirus Cell Entry. J Virol 89:8701-12|
Showing the most recent 10 out of 15 publications