PROJECT SUMMARY/ABSTRACT The Pandemic Assistance Core will enable investigators in this AViDD center to rapidly develop antiviral therapeutics for SARS-CoV-2 and other RNA viruses of pandemic potential. This core will provide capacity for rigorous in vitro and in vivo testing of compounds developed across all seven Projects, with a particular emphasis on providing unparalleled BSL3 and ABSL3 capacity. We will quickly and efficiently refine our targets and down-select from a series of go/no-go decisions over the course of our project, providing a funnelling structure to rapidly identify the most promising candidates both in vitro and in vivo. Compounds will be tested in both prophylactic and therapeutic models. As our Projects take unique approaches to target the viral life cycle, lead candidates from each project will also be tested in combination to identify synergism. The most promising of the lead candidates will then be sent for further development within the Translation Accelerator Core. To achieve this work we have brought together an outstanding and interdisciplinary team of investigators with significant experience in virology, drug development, and rodent models for drug screening. We also bring highly innovative approaches to test compounds in physiologic systems using human air-liquid interface (ALI) models and human adult lung organoids (ALO). We aim to provide industry-level capacity for screening and selecting the most promising drug candidates.