Figure 7.

LLPS Drives Temperature- and RNA Sequence-Dependent Packaging of the Viral Genome

Packaging of gRNA may be a temperature-dependent LLPS process driven by single-stranded regions flanked by structured regions (5′ end-like) that are stable N-protein binding sites. The majority of the genome resembles the solubilizing frameshifting region, while the region coding for N-protein is similar to the 5′ end. The balance between LLPS-promoting and solubilizing elements may facilitate gRNA packaging. Initial step of packaging (LLPS of N-protein with gRNA) may be targeted by compounds that either (1) induce condensate dissolution (1,6-hexanediol), (2) adjust condensate size through changes in kinetics or critical concentration (example kanamycin, lipoic acid), or (3) adjust protein/RNA ratio (example kanamycin).