Snapshots from simulations representing the release pathways. The rapid pathway category (R1–R3) was divided into (R1) burst genome release, where capsids disintegrate into fragments; (R2) rupture genome release, where capsids split open (most often into two halves); and (R3) bloom genome release, where capsids open wide in one hemisphere without breaking the other. In the rupture and bloom pathways, a majority of the capsid reassembles after the genome release. Occasionally, pentamers of capsid proteins may be detached. The subcategory leaky release (L) started with a slow release and ended with a rapid release. The slow pathway (S1–S3) category was divided into (S1) release through a pore on a twofold axis, (S2) release through a pore on a threefold axis, and (S3) release through multiple pores. Note that slow release was only observed for the noncompact genome. All release examples are shown with the noncompact genome. Color coding: Beads forming the body of the capsid are orange on the outside and purple on the inside of the capsid. The genome is represented by blue beads. Red and green beads represent attractive beads between pentamers.
Robert Vácha Research Group
Virus-like nanoparticles are protein shells similar to wild-type viruses, and both aim to deliver their content into a cell. Unfortunately, the release mechanism of their cargo/ genome remains elusive. Pores on the symmetry axes were proposed to enable the slow release of the viral genome. In contrast, cryo-EM images showed that capsids of nonenveloped RNA viruses can crack open and rapidly release the genome. We combined in vitro cryo-EM observations of the genome release of three viruses with coarse-grained simulations of generic virus-like nanoparticles to investigate the cargo/genome release pathways. Simulations provided details on both slow and rapid release pathways, including the success rates of individual releases. Moreover, the simulated structures from the rapid release pathway were in agreement with the experiment. Slow release occurred when interactions between capsid subunits were long-ranged, and the cargo/genome was noncompact. In contrast, rapid release was preferred when the interaction range was short and/or the cargo/genome was compact. These findings indicate a design strategy of virus-like nanoparticles for drug delivery.
Sukeník, L., Mukhamedova, L., Procházková, M., Škubník, K., Plevka, P., and Vácha, R.:
Cargo Release from Nonenveloped Viruses and Virus-like Nanoparticles: Capsid Rupture or Pore Formation, ABC Nano 2021, 15, 12, 19233–19243, https://doi.org/10.1021/acsnano.1c04814