Self-organizing synthetic human lungs on microchips to fight infection by RSV

Project Summary RSV is a major global threat that accounts for a significant share of respiratory disease and mortality among patients at risk. Infection by highly pathogenic RSV results in acute lung injury, LRTI, and pneumonia-associated complications. As treatments for RSV are very limited in use and efficacy, the development of physiological models of this disease is key to develop therapeutics that limit infection by this virus and associated pathology. This proposal will capitalize on RumiViro’s mini-lung platform that offers inexhaustible access to genetically matched organotypic human lung tissue to model infection by respiratory viruses. This platform will be deployed to model RSV infection in physiological lung tissue and identify therapeutics for this disease at scale. We will first screen a collection of 23,000 compounds of a highly diverse phenotypic library of bioactive compounds for their ability to mitigate infection by RSV. Hit candidates will be further validated for their ability to inhibit multiple clinical strains of RSV in mini- lungs and primary lung tissue ex vivo. This work will have transformative influence for the subsequent development of therapeutics and will enable further validation of therapeutic candidates based on drug metabolism, pharmacokinetic analysis, in vivo proof-of-concept and lead optimization efforts in follow-up Phase 2 studies. This work will provide a highly efficient framework for the identification and development of RSV therapeutics with the promise of finding anti-infective therapeutics that mitigate the RSV-induced pathology in patients at risk.