Influenza A virus liquid condensates can undergo pharmacological hardening

Multiple viral infections form biomolecular condensates in the host cell to facilitate viral replication. Accumulating evidence indicates that these viral condensates rely on specific material properties for function, but how these properties may be altered efficiently remains vastly unknown. Here, we use influenza A virus liquid cytosolic condensates, A.K.A viral inclusions, to provide a proof of concept that stabilizing transient interactions among the interactome in IAV inclusions more efficiently hardens these structures than varying temperature or concentration both in in situ and in in vivo models. This stabilization can be achieved by drug targeting, inducing changes in the solubility of viral proteome without affecting host cellular proteome. Our work supports the development of antivirals targeting the material properties of biomolecular condensates in viral infections. It also provides a framework for the efficient selection of pharmacological compounds with this activity and thus provides an advance in disease therapy.