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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.

SUBMITTER: Basta HA 

PROVIDER: S-EPMC3878079 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Modeling of the human rhinovirus C capsid suggests possible causes for antiviral drug resistance.

Basta Holly A HA   Ashraf Shamaila S   Sgro Jean-Yves JY   Bochkov Yury A YA   Gern James E JE   Palmenberg Ann C AC  

Virology 20131020


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  ...[more]

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