Pleconaril, a Novel Antipicornaviral Agent

Abstract

Despite the availability of therapy for selected symptoms, no specific antiviral agents are available to treat or prevent infections due to the viruses of the Picornaviridae family--rhinoviruses and enteroviruses. Characterization of the three-dimensional structure of picornaviruses in the 1980s allowed development of compounds targeted at the virus itself. Pleconaril is a novel, orally available, systemically acting molecule whose pharmacokinetics are characterized by a two-compartment open model with first-order absorption and with a safety profile similar to that of placebo. It shows promising results in treatment of picornaviral respiratory tract infections, meningitis, and other life-threatening infections.

Duration of Pleconaril Effect on Cytochrome P450 3a Activity in Healthy Adults Using the Oral Biomarker Midazolam

“…An open-label, single-sequence study design was used because of the prolonged elimination half-life of pleconaril (Florea et al, 2003). After an overnight fast, subjects were administered oral midazolam (0.075 mg/kg) on the morning of day 1 (baseline).…”

“…In healthy adults, oral pleconaril increases hepatic CYP3A activity after intravenous midazolam administration (Ma et al, 2006). Because of the prolonged half-life (ϳ180 h) of pleconaril (Rhodes and Liu, 2001a,b;Florea et al, 2003), the duration of increased CYP3A activity may be an important parameter in evaluating potential drug interactions with pleconaril. The purpose of this study was to evaluate the duration and extent of increased hepatic and intestinal CYP3A activity by pleconaril in healthy adults as assessed by oral midazolam.…”

“…Pleconaril antiviral activity is attributed to the disruption of viral replication and subsequent attenuation of viral attachment to the intercellular adhesion molecule 1 cellular receptor (Billich, 2000;Florea et al, 2003).…”

Potential Use of Antiviral Agents in Polio Eradication

“…Two of the most extensively characterized series of capsid-binding agents are the so-called WIN compounds, developed by Sterling Winthrop (New York, NY, USA), and a series of pyridazine analogs developed by the Janssen Research Foundation (Beerse, Belgium). The prototypes of these series are pleconaril (11) and pirodavir (12), respectively.…”

Antiviral Replication Agents

“…Characterization of the three-dimensional structure of picornaviruses in the 1980s allowed the development of compounds targeted at the virus itself (Florea et al, 2003). Pleconaril is known to be a broad spectrum anti-picornaviral agent that binds to a hydrophobic pocket in the viral capsid inducing conformational changes, which lead to altered receptor binding and viral uncoating (Romero, 2001).…”