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Related Concept Videos

Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...

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Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
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Open questions in enterovirus uncoating.

Walker Symonds-Orr1,2, Patrick T Dolan1,2

  • 1Quantitative Virology and Evolution Unit, Laboratory of Viral Diseases, NIH-NIAID Division of Intramural Research, Bethesda, Maryland, USA.

Journal of Virology
|May 15, 2026
PubMed
Summary

Enterovirus uncoating remains unclear. This review explores two models—genome translocation and particle escape—and discusses methods needed to resolve this viral entry mystery.

Keywords:
endosomesenterovirusespicornavirusvirion structurevirus entry

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Last Updated: May 17, 2026

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Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Enterovirus uncoating, the release of the viral RNA genome into the host cell cytoplasm, is a critical but poorly understood step in viral replication.
  • Understanding this process is key to developing antiviral strategies against enteroviruses, which cause a range of human diseases.

Purpose of the Study:

  • To review and critically evaluate the two main competing models for enterovirus uncoating: the genome translocation model and the particle escape model.
  • To outline the experimental approaches necessary to distinguish between these models and elucidate the precise mechanism of enterovirus genome release.

Main Methods:

  • Discussion of structural biology techniques to visualize virus-host interactions.
  • Review of in vitro reconstitution assays to study uncoating dynamics.
  • Analysis of cellular assays to track viral entry and genome release in infected cells.

Main Results:

  • The review presents a detailed comparison of the genome translocation model, proposing pore formation by viral proteins for RNA release, and the particle escape model, suggesting complete virion entry into the endosome before uncoating.
  • Highlights the limitations and strengths of current experimental evidence for each model.

Conclusions:

  • Definitively resolving the enterovirus uncoating mechanism requires a multidisciplinary approach combining structural, biochemical, and cellular studies.
  • Clarifying the uncoating process will provide crucial insights into viral entry and pathogenesis, potentially revealing new targets for antiviral therapies.