A High Throughput Screening Approach Enabling Sustainable Discovery of Novel Lead Compounds from Natural Product Extracts

Emerging drug resistance in infectious threats poses a health risk for deployed forces. The primary objective of the Phase I effort was to enable the development of a sustainable drug discovery effort to continually generate lead compounds for discovery and derivative synthesis. Successful completion of Phase I demonstrated the utilization of a novel source of lead compounds, validation of two high-throughput Plasmodium-targeted assays, and development of a custom Natural Extract Lead compound Identification (NELI) software platform. Phase II will build from Phase I by expanding the extract library to maximize biochemical diversity in the resultant extracts. A Gram-positive and Gram-negative high throughput assay will be developed for use with specified Plasmodium targets, along with a biomineral formation assay. Finally, the NELI software will be developed with the objective of enabling automated, determination of potential lead compounds. Dereplication will be accomplished by querying relevant databases. Development timelines are optimized to maximize utility of NELI to enable ƒnƒnƒÒ testing at select academic screening centers. Phase II effort will demonstrate the ability of the process to generate, extract, detect, and identify lead compounds present in natural product extracts. The final process will support WRAIR efforts in lead compound identification for infectious diseases.