Prevention of human poliovirus-induced paralysis and death in mice by the novel antiviral agent arildone.

Abstract

Arildone, a novel antiviral agent which blocks virion uncoating, was assessed for its ability to prevent paralysis and death in mice infected intracerebrally with a lethal dose of human poliovirus type-2 (strain MEF). Intraperitoneal administration of arildone suspended in gum tragacanth prevented paralysis and death in a dose-dependent manner (minimal inhibitory dose = 32 mg/kg, twice daily) and protected animals from virus challenges in excess of 20 50% lethal doses. Oral medication with arildone solubilized in corn oil was similarly effective in preventing poliovirus-induced paralysis and death. Arildone was therapeutically effective even when intraperitoneal medication was delayed for 48 h postinfection. Analysis of the virus titers in the central nervous system tissues of animals infected with 200 50% lethal doses demonstrated that arildone reduced titers in the brain and spine by approximately 3 and 4 log10 PFU per g of tissue, respectively, implying that direct inhibition of virus replication was responsible for host survival. Arildone is the first antiviral agent capable of preventing poliovirus-induced death in mice. The efficient inhibition of poliovirus replication described here demonstrates the potential usefulness of uncoating blockers in the systemic treatment of viral diseases.