This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pevear, D. C.
Right arrow Articles by Groarke, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pevear, D. C.
Right arrow Articles by Groarke, J. M.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 1999, p. 2109-2115, Vol. 43, No. 9
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Activity of Pleconaril against Enteroviruses

Daniel C. Pevear,* Tina M. Tull, Martin E. Seipel, and James M. Groarke

ViroPharma Incorporated, Exton, Pennsylvania

Received 3 March 1999/Returned for modification 17 May 1999/Accepted 14 June 1999

The activity of pleconaril in cell culture against prototypic enterovirus strains and 215 clinical isolates of the most commonly isolated enterovirus serotypes was examined. The latter viruses were isolated by the Centers for Disease Control and Prevention during the 1970s and 1980s from clinically ill subjects. Pleconaril at a concentration of <= 0.03 µM inhibited the replication of 50% of all clinical isolates tested. Ninety percent of the isolates were inhibited at a drug concentration of <= 0.18 µM. The most sensitive serotype, echovirus serotype 11, was also the most prevalent enterovirus in the United States from 1970 to 1983. Pleconaril was further tested for oral activity in three animal models of lethal enterovirus infection: coxsackievirus serotype A9 infection in suckling mice, coxsackievirus serotype A21 strain Kenny infection in weanling mice, and coxsackievirus serotype B3 strain M infection in adult mice. Treatment with pleconaril increased the survival rate in all three models for both prophylactic and therapeutic dosing regimens. Moreover, pleconaril dramatically reduced virus levels in target tissues of coxsackievirus serotype B3 strain M-infected animals. Pleconaril represents a promising new drug candidate for potential use in the treatment of human enteroviral infections.

* Corresponding author. Mailing address: ViroPharma Incorporated, 405 Eagleview Blvd., Exton, PA 19341. Phone: (610) 458-7300, ext. 110. Fax: (610) 458-7380. E-mail: dpevear{at}viropharma.com.

Antimicrobial Agents and Chemotherapy, September 1999, p. 2109-2115, Vol. 43, No. 9
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Oberste, M. S., Moore, D., Anderson, B., Pallansch, M. A., Pevear, D. C., Collett, M. S. (2009). In Vitro Antiviral Activity of V-073 against Polioviruses. Antimicrob. Agents Chemother. 53: 4501-4503 [Abstract] [Full Text]  
  • Chen, T.-C., Weng, K.-F., Chang, S.-C., Lin, J.-Y., Huang, P.-N., Shih, S.-R. (2008). Development of antiviral agents for enteroviruses. J Antimicrob Chemother 62: 1169-1173 [Abstract] [Full Text]  
  • Brunetti, L., DeSantis, E. R. H. (2008). Treatment of viral myocarditis caused by coxsackievirus B. Am J Health Syst Pharm 65: 132-137 [Abstract] [Full Text]  
  • Lanke, K., Krenn, B. M., Melchers, W. J. G., Seipelt, J., van Kuppeveld, F. J. M. (2007). PDTC inhibits picornavirus polyprotein processing and RNA replication by transporting zinc ions into cells. J. Gen. Virol. 88: 1206-1217 [Abstract] [Full Text]  
  • Desmond, R. A., Accortt, N. A., Talley, L., Villano, S. A., Soong, S.-J., Whitley, R. J. (2006). Enteroviral meningitis: natural history and outcome of pleconaril therapy.. Antimicrob. Agents Chemother. 50: 2409-2414 [Abstract] [Full Text]  
  • Ma, J. D., Nafziger, A. N., Rhodes, G., Liu, S., Gartung, A. M., Bertino, J. S. Jr (2006). The Effect of Oral Pleconaril on Hepatic Cytochrome P450 3A Activity in Healthy Adults Using Intravenous Midazolam as a Probe. J Clin Pharmacol 46: 103-108 [Abstract] [Full Text]  
  • Schmidtke, M., Hammerschmidt, E., Schuler, S., Zell, R., Birch-Hirschfeld, E., Makarov, V. A., Riabova, O. B., Wutzler, P. (2005). Susceptibility of coxsackievirus B3 laboratory strains and clinical isolates to the capsid function inhibitor pleconaril: antiviral studies with virus chimeras demonstrate the crucial role of amino acid 1092 in treatment. J Antimicrob Chemother 56: 648-656 [Abstract] [Full Text]  
  • Makarov, V. A., Riabova, O. B., Granik, V. G., Wutzler, P., Schmidtke, M. (2005). Novel [(biphenyloxy)propyl]isoxazole derivatives for inhibition of human rhinovirus 2 and coxsackievirus B3 replication. J Antimicrob Chemother 55: 483-488 [Abstract] [Full Text]  
  • Shih, S.-R., Tsai, M.-C., Tseng, S.-N., Won, K.-F., Shia, K.-S., Li, W.-T., Chern, J.-H., Chen, G.-W., Lee, C.-C., Lee, Y.-C., Peng, K.-C., Chao, Y.-S. (2004). Mutation in Enterovirus 71 Capsid Protein VP1 Confers Resistance to the Inhibitory Effects of Pyridyl Imidazolidinone. Antimicrob. Agents Chemother. 48: 3523-3529 [Abstract] [Full Text]  
  • Salvati, A. L., De Dominicis, A., Tait, S., Canitano, A., Lahm, A., Fiore, L. (2004). Mechanism of Action at the Molecular Level of the Antiviral Drug 3(2H)-Isoflavene against Type 2 Poliovirus. Antimicrob. Agents Chemother. 48: 2233-2243 [Abstract] [Full Text]  
  • Barnard, D. L., Hubbard, V. D., Smee, D. F., Sidwell, R. W., Watson, K. G. W., Tucker, S. P. T., Reece, P. A. R. (2004). In Vitro Activity of Expanded-Spectrum Pyridazinyl Oxime Ethers Related to Pirodavir: Novel Capsid-Binding Inhibitors with Potent Antipicornavirus Activity. Antimicrob. Agents Chemother. 48: 1766-1772 [Abstract] [Full Text]  
  • Buttinelli, G., Donati, V., Fiore, S., Marturano, J., Plebani, A., Balestri, P., Soresina, A. R., Vivarelli, R., Delpeyroux, F., Martin, J., Fiore, L. (2003). Nucleotide variation in Sabin type 2 poliovirus from an immunodeficient patient with poliomyelitis. J. Gen. Virol. 84: 1215-1221 [Abstract] [Full Text]  
  • (2000). Enterovirus Surveillance--United States, 1997-1999. JAMA 284: 2311-2312 [Full Text]  
  • Rotbart, H. A., Hayden, F. G. (2000). Picornavirus Infections: A Primer for the Practitioner. Arch Fam Med 9: 913-920 [Abstract] [Full Text]  
  • Temte, J. L. (2000). A Family Physician's Perspective on Picornavirus Infections in Primary Care. Arch Fam Med 9: 921-922 [Full Text]  
  • Yarush, L. I., Steele, R. W. (2000). Editorial: Diagnosis and Prospective Treatment of Enteroviral Infections in Children. CLIN PEDIATR 39: 209-211  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»