PROGRAM SUMMARY/ABSTRACT Emerging viruses arise suddenly and cause considerable morbidity and mortality worldwide. To prepare for current and future threats, public-private partnerships are needed to change the current reactive response platform into one that is proactive. In response to RFA-AI-21-050, the Rapidly Emerging Antiviral Drug Development Initiatives AViDD Center (READDI-AC) is an integrated public-private partnership with a renowned, interdisciplinary research team of experts, who apply cutting edge innovative technologies in virology, biochemistry, structural biology, medicinal chemistry, computational biology, structure-guided drug design and genomics to develop oral, potent, broad-spectrum family-specific antivirals for coronaviruses, flaviviruses, alphaviruses and filoviruses. To achieve these goals, the READDI-AC program includes academic leaders in basic and applied antiviral research and chemistry as well as industry leaders Janssen Pharmaceuticals N.V.(JPNV), Takeda, Chimerix Inc. and Pardes Biosciences. Our commercial partners provide an enviable track records in drug discovery and product development, and leadership in medicinal chemistry, pharmacology, drug formulation, toxicity studies and pharmacokinetics, especially critical for driving optimized leads through preIND enabling studies toward the clinic. Importantly, our industry partners also provide in kind matching contributions, access to high quality commercial chemical libraries, early hits, optimized leads, and state of the art high- throughput screens. The immediate and long-term goals of READDI-AC are to: a) validate druggable targets in conserved viral proteins, b) identify hits and leads using SAR and state of the art biochemical and enzymatic assays, c) optimize/formulate chemical probes and lead compounds as broadly acting oral compounds with activity against multiple relevant members of each emerging virus family; d) provide critical late-stage preclinical development and IND-enabling in vivo studies for two broadly active, oral drug candidates; e) promote open science sharing of unused chemical assets, chemical probes, methods, reagents and assays for innovations by crowdsourcing; f) build capacity and training in 21st century viral drug discovery and development by coupling innovative approaches in target discovery and validation with state of the art techniques, integrated workflows and novel discovery platforms for hit to lead progression and SAR optimization. READDI-AC has five Research Projects and four highly interactive cores that establish a cooperative landscape that builds leadership, expertise, response capacity and partnerships that invigorate 21st century drug development.