Pleconaril: a novel antipicornaviral drug

Pleconaril (VP-63843) 3-[3,5-dimethyl-4[[3-(3-methyl-5-isoxazo oly]phenyl]- 5-(trifluoromethyl)-1,2,4-oxa is a novel, broad spectrum antipicornaviral a gent. Pleconaril binds to a hydrophobic pocket in the viral capsid inducing conformational changes, which lead to altered receptor binding and viral u ncoating. Pleconaril is orally bioavailable and achieves serum concentratio ns in excess of those required to inhibit 90% of clinical rhino- and entero viral isolates in vitro. It possesses the additional advantage of achieving several fold higher concentrations within the central nervous system and n asal secretions than in serum, a characteristic that is highly desirable fo r an antiviral targeted towards viruses known to cause central nervous syst em and upper respiratory tract infections. Approximately 80% of an orally a dministered dose is excreted in the faeces within 48 h. Urine excretion acc ounts for the remainder of the drug. Pleconaril has demonstrated an excelle nt safety profile in dose escalation and clinical studies. Clinical studies have reported a reduction in the duration and intensity of symptoms in chi ldren and adults with enteroviral meningitis and in adults with rhinoviral respiratory tract infections treated with pleconaril. Lastly, pleconaril ha s demonstrated efficacy in the treatment of severe life-threatening enterov iral infections of the newborn and in immunosuppressed individuals. Plecona ril appears to be a promising drug for the treatment of enteroviral and rhi noviral infections.