Understanding the human health importance of pathogen surveillance data is not currently possible from sequence or other molecular information alone. The Closing the Doors to All Pathogens Through Integrated Digital Experiments (DOORs) project aims to 1) Create a comprehensive computational map of pathogen-host interactions, 2) Uncover the best drug targets for an entire family of pathogens, instead of each individual pathogen as it’s done today, and 3) Test approved therapies and discover new ones via computer models. The vision for DOORs is to protect U.S. national security from emerging biological threats with an integrated digital experimental workflow that closes the loop for detecting, understanding, and responding to infectious diseases, while making these activities commercially viable through host-based therapeutic discovery.