Activity of pleconaril against enteroviruses

The activity of pleconaril in cell culture against prototypic enterovirus s trains 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 less than or equal to 0.03 m u M inhibited the replication of 50% of all clinical isolates tested. Ninet y percent of the isolates were inhibited at a drug concentration of less th an or equal to 0.18 mu M 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 mode ls of lethal enterovirus infection: coxsackievirus serotype A9 infection in suckling mice, coxsackievirus serotype A21 strain Kenny infection in weanl ing mice, and coxsackievirus serotype B3 strain hi 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 sero type B3 strain M-infected animals. Pleconaril represents a promising new dr ug candidate for potential use in the treatment of human enteroviral infect ions.