RT Journal Article SR Electronic T1 Rules for hardening influenza A virus liquid condensates JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.08.03.502602 DO 10.1101/2022.08.03.502602 A1 Temitope Akhigbe Etibor A1 Sílvia Vale-Costa A1 Sindhuja Sridharan A1 Daniela Brás A1 Isabelle Becher A1 Victor Hugo Mello A1 Filipe Ferreira A1 Marta Alenquer A1 Mikhail M Savitski A1 Maria João Amorim YR 2022 UL http://biorxiv.org/content/early/2022/11/07/2022.08.03.502602.abstract AB Multiple viral infections form biomolecular condensates in the host cell to compartmentalize viral reactions. Accumulating evidence indicates that these viral condensates may be hardened, a strategy with potential for exploitation as novel antiviral therapy, given that viral reactions rely on specific material properties for function. However, there is no molecular understanding on how to specifically and efficiently modify the material properties of viral condensates, a pre-requisite for overcoming off-target effects by rational drug design. In vitro, the material properties of biological condensates are modified by different thermodynamic parameters, including free energy, concentration, and type/strength of interactions. Here, we used influenza A virus liquid cytosolic condensates, A.K.A viral inclusions, to provide a proof of concept that modulating the type/strength of transient interactions among the interactome in IAV inclusions is more efficient at hardening these structures than varying the temperature or concentration, both in in vitro and in in vivo models. This stabilization can be achieved by a known pharmacological sticker that can specifically change the material properties of viral inclusions without affecting host proteome abundance nor solubility. Our work supports the development of antivirals targeting the material properties of biomolecular condensates in viral infections. It also provides a framework for the selection of compounds with this activity for general application and thus provides an advance in disease therapy.Competing Interest StatementThe authors have declared no competing interest.