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Journal of Virology, October 2004, p. 11061-11069, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11061-11069.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Ying Zhang,1 Alan A. Simpson,1 Rebecca M. Ledford,2 Carol M. Bator,1 Sugoto Chakravarty,1,{dagger} Gregory A. Skochko,2 Tina M. Demenczuk,2 Adiba Watanyar,2 Daniel C. Pevear,2 and Michael G. Rossmann1*

Department of Biological Sciences, Purdue University, West Lafayette, Indiana,1 ViroPharma Incorporated, Exton, Pennsylvania2

Received 21 May 2003/ Accepted 17 June 2004

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.

* Corresponding author. Mailing address: Department of Biological Sciences, Lilly Hall, Purdue University, 915 W. State St., West Lafayette, IN 47907-2054. Phone: (765) 494-4911. Fax: (765) 496-1189. E-mail: mgr{at}indiana.bio.purdue.edu.

{dagger} Present address: Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030.

Journal of Virology, October 2004, p. 11061-11069, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11061-11069.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pevear, D. C., Hayden, F. G., Demenczuk, T. M., Barone, L. R., McKinlay, M. A., Collett, M. S. (2005). Relationship of Pleconaril Susceptibility and Clinical Outcomes in Treatment of Common Colds Caused by Rhinoviruses. Antimicrob. Agents Chemother. 49: 4492-4499 [Abstract] [Full Text]  
  • Li, Y., Zhou, Z., Post, C. B. (2005). From the Cover: Dissociation of an antiviral compound from the internal pocket of human rhinovirus 14 capsid. Proc. Natl. Acad. Sci. USA 102: 7529-7534 [Abstract] [Full Text]  


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