Identification of a conserved virion-stabilizing network inside the interprotomer pocket of enteroviruses

Commun Biol. 2021 Feb 26;4(1):250. doi: 10.1038/s42003-021-01779-x.


Enteroviruses pose a persistent and widespread threat to human physical health, with no specific treatments available. Small molecule capsid binders have the potential to be developed as antivirals that prevent virus attachment and entry into host cells. To aid with broad-range drug development, we report here structures of coxsackieviruses B3 and B4 bound to different interprotomer-targeting capsid binders using single-particle cryo-EM. The EM density maps are beyond 3 Å resolution, providing detailed information about interactions in the ligand-binding pocket. Comparative analysis revealed the residues that form a conserved virion-stabilizing network at the interprotomer site, and showed the small molecule properties that allow anchoring in the pocket to inhibit virus disassembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Binding Sites
  • Capsid / drug effects*
  • Capsid / metabolism
  • Capsid / ultrastructure
  • Capsid Proteins / metabolism*
  • Capsid Proteins / ultrastructure
  • Cell Line
  • Chlorocebus aethiops
  • Cryoelectron Microscopy
  • Drug Development
  • Enterovirus B, Human / drug effects*
  • Enterovirus B, Human / metabolism
  • Enterovirus B, Human / ultrastructure
  • Ligands
  • Molecular Docking Simulation
  • Protein Conformation
  • Virus Assembly / drug effects*


  • Antiviral Agents
  • Capsid Proteins
  • Ligands