(66o) Computational Modelling of Condensate-Mediated Viral Capsid Assembly and Genome Packaging

Biomolecular condensates formed by liquid-liquid phase separation have recently emerged as a powerful means to compartmentalize and regulate cellular processes. Many viruses create condensates within their host cells, potentially enabling control over viral replication and assembly in space and time. Yet, the mechanisms by which condensates facilitate assembly are not well understood. Here, we develop computational models to investigate how selective partitioning of viral components into condensates affects assembly and genome packaging. Using a master equation model, we find that condensates can both greatly enhance selective genome packaging and increase the rate and yield of capsid assembly by orders of magnitude. Moreover, recent work has shown that some viral condensates recruit ribosomes, and we show that the resulting localized production of capsid subunits can further enhance packaging selectivity. Furthermore, with coarse-grained molecular dynamics simulations, we find that viral condensates can control the number of assembled capsids and create classes of assembly pathways that are unseen in cytoplasmic assembly. Our work suggests that condensates can be a powerful means to facilitate capsid assembly and genome packaging, and hence are potential antiviral drug targets. More broadly, the mechanisms that we have identified could facilitate rapid and selective cargo encapsulation in diverse biological or human-engineered systems.