Enteroviruses can cause persistent central nervous system (
CNS) infections in agammaglobulinemic individuals. Because these
infections are rarely cured by passive administration of antibody, a chemotherapeutic approach would be advantageous. In this study, the efficacy of the antienterovirus (and antipicornavirus)
drug disoxaril was demonstrated in a murine model of persistent
enterovirus infection.
Disoxaril is a hydrophobic
antiviral compound that blocks picornavirus uncoating. The W-2 strain of human poliovirus type 2 (PV2) persists in the CNS of immunosuppressed mice and causes late
paralysis. Mice were inoculated intracerebrally with PV2, immunosuppressed with
cyclophosphamide, and treated intragastrically with
disoxaril at 50, 100, or 200 mg/kg per day in two divided doses beginning on postinfection day 20. At 200 mg/kg per day,
disoxaril significantly decreased the incidence of clinical disease, i.e.,
paralysis and death. Assays for virus revealed more rapid clearance of virus from the CNS in the
drug-treated group. No
drug-associated toxicity was observed. Residual isolates of virus were not
drug-resistant, suggesting that the appearance of drug resistance during prolonged treatment may not be a clinical problem.