Cargo Release from Nonenveloped Viruses and Virus-like Nanoparticles: Capsid Rupture or Pore Formation

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Authors

SUKENÍK Lukáš MUKHAMEDOVA Liya PROCHÁZKOVÁ Michaela ŠKUBNÍK Karel PLEVKA Pavel VÁCHA Robert

Year of publication 2021
Type Article in Periodical
Magazine / Source ACS Nano
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://pubs.acs.org/doi/10.1021/acsnano.1c04814
Doi http://dx.doi.org/10.1021/acsnano.1c04814
Keywords virus-like nanoparticlesRNA virusgenome releasecapsidcomputer simulationscoarse-grained modelcryo-EM
Description 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.
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