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Solvent ordering in a fully packaged RNA bacteriophage and the mechanics of genome delivery

Coshic, K.; Kumari, M.; Aksimentiev, A.

2026-05-29 biophysics
10.64898/2026.05.27.727985 bioRxiv
Show abstract

Self-assembly of an RNA virus requires a thermodynamic state stable enough to confine the highly charged genome yet primed for genome delivery. By simulating the behavior of every atom in a packaged bacteriophage, we determined the physical factors enabling such a state to emerge. We show that the electrical charge of the RNA genome is neutralized by both a cloud of mobile counterions and polarized water that exhibits a long-range order despite stochastic motion of the unstructured parts of the genome. Acting as an intermolecular glue, the solvent equipoises self-repulsion of the RNA genome with attraction of RNA to specific sites at the capsid, accommodating the mechanical stress produced by the capsids fluctuations. Simulations of genome extraction show that specific RNA-protein contacts can withstand extreme forces, supporting mechanical extraction as a mechanism of genome delivery. Together, our findings detail how self-assembled viruses balance the conflicting biophysical demands of confinement and infection.

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