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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.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.