title: Modeling of the human rhinovirus C capsid suggests possible causes for antiviral drug resistance.
abstract: Human rhinoviruses of the RV-C species are recently discovered pathogens with greater clinical significance than isolates in the RV-A+B species. The RV-C cannot be propagated in typical culture systems; so much of the virology is necessarily derivative, relying on comparative genomics, relative to the better studied RV-A+B. We developed a bioinformatics-based structural model for a C15 isolate. The model showed the VP1-3 capsid proteins retain their fundamental cores relative to the RV-A+B, but conserved, internal RV-C residues affect the shape and charge of the VP1 hydrophobic pocket that confers antiviral drug susceptibility. When predictions of the model were tested in organ cultures or ALI systems with recombinant C15 virus, there was a resistance to capsid-binding drugs, including pleconaril, BTA-188, WIN56291, WIN52035 and WIN52084. Unique to all RV-C, the model predicts conserved amino acids within the pocket and capsid surface pore leading to the pocket may correlate with this activity.
authors: Institute for Molecular Virology, University of Wisconsin, 1525 Linden Drive, Madison, WI 53706, United States of America.
authors: Holly A
authors: HA
authors: Basta
authors: Shamaila
authors: S
authors: Ashraf
authors: Jean-Yves
authors: JY
authors: Sgro
authors: Yury A
authors: YA
authors: Bochkov
authors: James E
authors: JE
authors: Gern
authors: Ann C
authors: AC
authors: Palmenberg
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002213:Capsid / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024882:Drug Resistance, Viral; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010850:Picornaviridae Infections / Q000821:virology; D012229:Rhinovirus / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D000998:Antiviral Agents; D036022:Capsid Proteins
keywords: Antiviral therapy; Capsid structure; Drug resistance; Drug-binding pocket; Model; Pleconaril; Pore; Rhinovirus; Rhinovirus C