Core A

Administrative Core

PI: Richard J. Whitley, University of Alabama at Birmingham

The Administrative Core of the Antiviral Drug Discovery and Development Center (AD3C) provides a key role in leadership, communication, coordination and oversight of the projects and cores, and stimulate collaboration and synergy between the projects. Operationally, it is in charge of fiscal and contractual management of the center and plans and implements activities, such as meetings of the Executive Committee (EC), external Scientific Advisory Committee (SAC), and an annual meeting of all projects and cores. In addition, it manages the inter-institutional cooperative agreements. Finally, the core facilitates dissemination of progress and discoveries to the public.

Core B

Assay Core

PI: J. Robert Bostwick, Southern Research

The Assay Core B will be led by Dr. Robert Bostwick (SR) and will perform the assays needed by the MCLDC to develop the structure-activity relationships (SAR) for each project to ensure a timely turnaround of the biological data. This will require an integrated approach and information sharing between the Assay Core and the Projects as well as between the Assay Core and MCLDC. The Assay Core also will provide resources to assist with other assays that may be needed by the individual Project investigators, as this core group has extensive experience in the development and miniaturization of cell-based and biochemical assays, as well as automation, compound management and bioinformatics experience across a wide variety of assay types. The Assay Core has the ability to conduct experiments at BSL-2 and BSL-3 containment as required for these assays. All assays needed to support the medicinal chemistry efforts for the viruses in this program are already established and validated at the Assay Core.

Core C

Medicinal Chemistry and Lead Development Core

PI: Ashish K. Pathak, Southern Research

The MCLDC, in conjunction with the Assay Core, is led by Drs. Ashish Pathak, Corinne Augelli-Szafran andMark Suto (SR) and by Drs. George Painter and Gregory Bluemling (Emory Institute for Drug Development). In conjunction with the Assay Core, it will be the central focus of the translational research component of the program. Lead molecules will be generated to develop potential drug candidates with optimized biological and biophysical properties for the treatment of emerging viral pathogens. The MCLDC will work very closely and collaboratively with all Research Projects and Core Leads. In our prior CETR, the MCLDC provided the highthroughput screening data analyses regarding hit identification, hit-to-lead analysis, synthetic chemistry, and structure-activity relationship (SAR), as well as computational and structural biology support, pharmacokinetic support and lead optimization chemistry. In this CETR application, a comprehensive project plan has been crafted that involves all Core sites, including lead compound profiling for a particular target, a workflow structure, timelines, key milestones and deliverables, as well as “Go/No-Go” decision points. Decisions about the specific biological assays will be used to inform the SAR, and the type and extent of optimization appropriate for each given compound or chemical series are expected to vary according to project. These decisions are made in conjunction with the Project and Core Leaders, and the remainder of the CETR project team. Lead compounds will be provided to the various Research Project teams for advanced studies, of which the resulting data will be analyzed by the MCLDC to drive the iterative drug discovery program to completion. Regularly scheduled discussions among members of the Assay Core and Research Project teams will facilitate the prioritization of MCLDC efforts and decisions.