Structural analysis of antiviral agents that interact with the capsid of human rhinoviruses

John Badger, Iwona Minor, Macros A. Oliveira, Thomas J. Smith, Michael G. Rossmann

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


X‐Ray diffraction data have been obtained for nine related antiviral agents (“WIN compounds”) while bound to human rhinovirus 14 (HRV14).These compounds can inhibit both viral attachment to host cells and uncoating. To calculate interpretable electron density maps it was necessary to account for (1) the low (∼60percnt;) occupancies of these compounds in the crystal, (2) the large (up to 7.9 Å) conformational changes induced at the attachment site, and (3) the incomplete diffraction data. Application of a density difference map technique, which exploits the 20‐fold noncrystallographic redundancy in HRV14, resulted in clear images of the HRV14:WIN complexes. A real‐space refinement procedure was used to fit atomic models to these maps. The binding site of WIN compounds in HRV14 is a hydrophobic pocket composed mainly from residues that form the β‐barrel of VP1. Among rhinoviruses, the residues associated with the binding pocket are far more conserved than external residues and are mostly contained within regular secondary structural elements. Molecular dynamics simulations of three HRV14:WIN complexes suggest that portions of the WIN compounds and viral protein near the entrance of the binding pocket are more flexible than portions deeper within the β‐barrel.

Original languageEnglish (US)
Pages (from-to)1-19
Number of pages19
JournalProteins: Structure, Function, and Bioinformatics
Issue number1
StatePublished - 1989
Externally publishedYes


  • antiviral agents
  • hydrophobic pockets
  • molecular dynamics
  • virus crystallography

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology


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