Structural and Virological Studies of the Stages of Virus Replication That Are Affected by Antirhinovirus Compounds

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2004 Sep 29

PMID 15452226

Citations 30

Authors

Ying Zhang

Alan A Simpson

Rebecca M Ledford

Carol M Bator

Sugoto Chakravarty

Gregory A Skochko

Tina M Demenczuk

Adiba Watanyar

Daniel C Pevear

Michael G Rossmann

Affiliations

Soon will be listed here.

Abstract

Pleconaril is a broad-spectrum antirhinovirus and antienterovirus compound that binds into a hydrophobic pocket within viral protein 1, stabilizing the capsid and resulting in the inhibition of cell attachment and RNA uncoating. When crystals of human rhinovirus 16 (HRV16) and HRV14 are incubated with pleconaril, drug occupancy in the binding pocket is lower than when pleconaril is introduced during assembly prior to crystallization. This effect is far more marked in HRV16 than in HRV14 and is more marked with pleconaril than with other compounds. These observations are consistent with virus yield inhibition studies and radiolabeled drug binding studies showing that the antiviral effect of pleconaril against HRV16 is greater on the infectivity of progeny virions than the parent input viruses. These data suggest that drug integration into the binding pocket during assembly, or at some other late stage in virus replication, may contribute to the antiviral activity of capsid binding compounds.

Citing Articles

Cryo-EM of human rhinovirus reveals capsid-RNA duplex interactions that provide insights into virus assembly and genome uncoating.

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Within-Host Rhinovirus Evolution in Upper and Lower Respiratory Tract Highlights Capsid Variability and Mutation-Independent Compartmentalization.

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Within-host rhinovirus evolution in upper and lower respiratory tract highlights capsid variability and mutation-independent compartmentalization.

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Rhinovirus Inhibitors: Including a New Target, the Viral RNA.

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