Persistent infections with a cardiotropic enterovirus, e.g. coxsackievirus B2 (CVB2), cause chronic
myocarditis and eventually
congestive heart failure. Therefore, the
antiviral activity of
WIN 54954, a capsid binding
antiviral agent that inhibits enterovirus uncoating, was studied in persistently CVB2-infected cultures of human myocardial fibroblasts. Cultures displayed a typical carrier state
infection with virus titers of 3.9 +/- 1.6 x 10(5) plaque forming units (PFU)/ml and 0.99% infected cells.
WIN 54954 (0.025-1 microg/ml) application was started 7 days after
infection of the cultures. Compared to the
WIN 54954 concentration resulting in a 90% plaque number reduction (EC90 = 0.197 microg/ml) in acutely infected Vero cells,
WIN 54954 reduced virus yields of myocardial fibroblast cultures more efficiently, e.g. more than 100 fold (99%) with 0.025 microg/ml after 4 days of application.
Antiviral effects of
WIN 54954 increased with application time and at 0.025 microg/ml
Win 54954 completely inhibited infectious virus progeny after 16 days. Increasing the
WIN 54954 concentration up to 1 microg/ml did not cause a greater inhibition of virus replication. In situ hybridization demonstrated that at 0.1 microg/ml
WIN 54954 reduced the number of infected cells from 0.99 to 0.18%, although a complete eradication of CVB2-infected cells was not achieved at concentrations as high as 1 microg/ml. In conclusion, the results indicate that low concentrations of
WIN 54954 are effective in treating persistent
enterovirus infections of myocardial fibroblasts, although a complete eradication of the
infection is not achieved with
WIN 54954 as a single
antiviral agent.