ArticleProceedings of the National Academy of Sciences of the United States of America2014
Solving a Levinthal's paradox for virus assembly identifies a unique antiviral strategy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 120 citations in OpenAlex.
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- From disorder to icosahedral symmetry: How conformation-switching subunits enable RNA virus assembly.Science advances · 2025Article
- Measuring the selective packaging of RNA molecules by viral coat proteins in cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Disassembly of Virus-Like Particles and the Stabilizing Role of the Nucleic Acid Cargo.The journal of physical chemistry. B · 2025Article
- Review
- Molecular Dynamics Characterization of the Free and Encapsidated RNA2 of CCMV with the oxRNA Model.Macromolecular rapid communications · 2024Article
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- Synthesis, insertion, and characterization of SARS-CoV-2 membrane protein within lipid bilayers.Science advances · 2024Article
- Effect of ionic strength on the assembly of simian vacuolating virus capsid protein around poly(styrene sulfonate).The European physical journal. E, Soft matter · 2023Article
- Single-particle studies of the effects of RNA-protein interactions on the self-assembly of RNA virus particles.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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- Microcompartment assembly around multicomponent fluid cargoes.The Journal of chemical physics · 2022Article
- Applications of Charge Detection Mass Spectrometry in Molecular Biology and Biotechnology.Chemical reviews · 2022Review
- Programmable polymorphism of a virus-like particle.Communications materials · 2022Article
- In vitro functional analysis of gRNA sites regulating assembly of hepatitis B virus.Communications biology · 2021Article
- Therapeutic interfering particles exploiting viral replication and assembly mechanisms show promising performance: a modelling study.Scientific reports · 2021Article
- The impact of local assembly rules on RNA packaging in a T = 1 satellite plant virus.PLoS computational biology · 2021Article
- Article
- Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein.Science (New York, N.Y.) · 2021Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
One of the important puzzles in virology is how viruses assemble the protein containers that package their genomes rapidly and efficiently in vivo while avoiding triggering their hosts' antiviral defenses. Viral assembly appears directed toward a relatively small subset of the vast number of all possible assembly intermediates and pathways, akin to Levinthal's paradox for the folding of polypeptide chains. Using an in silico assembly model, we demonstrate that this reduction in complexity can be understood if aspects of in vivo assembly, which have mostly been neglected in in vitro experimental and theoretical modeling assembly studies, are included in the analysis. In particular, we show that the increasing viral coat protein concentration that occurs in infected cells plays unexpected and vital roles in avoiding potential kinetic assembly traps, significantly reducing the number of assembly pathways and assembly initiation sites, and resulting in enhanced assembly efficiency and genome packaging specificity. Because capsid assembly is a vital determinant of the overall fitness of a virus in the infection process, these insights have important consequences for our understanding of how selection impacts on the evolution of viral quasispecies. These results moreover suggest strategies for optimizing the production of protein nanocontainers for drug delivery and of virus-like particles for vaccination. We demonstrate here in silico that drugs targeting the specific RNA-capsid protein contacts can delay assembly, reduce viral load, and lead to an increase of misencapsidation of cellular RNAs, hence opening up unique avenues for antiviral therapy.
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