The focus of this Center grant application Is to develop small molecule therapeutics targeting filovirus Innate immune antagonists and viral transcription functions. The expectation is that small molecule inhibitors of each target will independently suppress virus replication and exert a therapeutic effect. However, because each inhibitor will have a different mechanism of action and a different target, combinations of inhibitors are expected to exert synergistic antiviral effects. To achieve these goals, we have assembled a team from multiple institutions and diverse backgrounds In filovirus biology. Innate Immunity, structural biology, antiviral drug development and medicinal chemistry. It will be the role of the Administrative Core to provide the necessary oversight, guidance, support and services to ensure the maximal productivity and effective Integration of the efforts of each project and scientific core. The Administrative Core first of all will manage the Center by coordinating financial reporting, submission of progress reports, and other regulatory reports, ensure compliance with regulatory issues, assist with manuscript publication and oversee scientific direction. The latter will include the recruitment of and communication with the scientific advisory board. The Administrative Core will also coordinate participation of project participants to the annual National CETR Program Meeting and a separate annual reverse site visit with NIAID;arrange an Annual Meeting among members of all participating groups, to be held at one of the participating sites;schedule monthly web-based Interlab virtual meetings to exchange ideas and critique data;arrange bi-weekly teleconferences between the Pis and maintain an infrastructure for Web-based resources. Data Management and Data Sharing. To ensure efficient use of the Biosafety Level 4 Core (Core B), which will conduct antiviral testing against Ebola and Marburg viruses, the Administrative Core will provide a formal committee to oversee and ensure efficient use of this Core. Finally, the Administrative Core will oversee and implement a process to solicit, evaluate and recommend Supplemental Research Project applications

Public Health Relevance

): Ebola and Marburg viruses cause a highly lethal hemorrhagic fever and are of concern as potential bioweapons. Core A will provide administrative oversite of this Center so as to promote the development of inhibitors targeting the filovirus innate Immune evasion and transcription functions as anti-filoviral therapies

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-LR-M (J1))
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Icahn School of Medicine at Mount Sinai
New York
United States
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Esposito, Anthony M; Cheung, Pamela; Swartz, Talia H et al. (2016) A high throughput Cre-lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry. Virology 490:6-16
Pleet, Michelle L; Mathiesen, Allison; DeMarino, Catherine et al. (2016) Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction. Front Microbiol 7:1765
Leung, Daisy W; Amarasinghe, Gaya K (2016) When your cap matters: structural insights into self vs non-self recognition of 5' RNA by immunomodulatory host proteins. Curr Opin Struct Biol 36:133-41
Baer, Alan; Shafagati, Nazly; Benedict, Ashwini et al. (2016) Protein Phosphatase-1 regulates Rift Valley fever virus replication. Antiviral Res 127:79-89
Edwards, Megan R; Liu, Gai; Mire, Chad E et al. (2016) Differential Regulation of Interferon Responses by Ebola and Marburg Virus VP35 Proteins. Cell Rep 14:1632-40
Rialdi, Alex; Campisi, Laura; Zhao, Nan et al. (2016) Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation. Science 352:aad7993
Chatterjee, Srirupa; Basler, Christopher F; Amarasinghe, Gaya K et al. (2016) Molecular Mechanisms of Innate Immune Inhibition by Non-Segmented Negative-Sense RNA Viruses. J Mol Biol 428:3467-82
Basler, Christopher F (2015) Innate immune evasion by filoviruses. Virology 479-480:122-30
Messaoudi, Ilhem; Basler, Christopher F (2015) Immunological features underlying viral hemorrhagic fevers. Curr Opin Immunol 36:38-46
Edwards, Megan R; Pietzsch, Colette; Vausselin, Thibaut et al. (2015) High-Throughput Minigenome System for Identifying Small-Molecule Inhibitors of Ebola Virus Replication. ACS Infect Dis 1:380-7

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