Pleconaril: a novel antipicornaviral drug.
Pleconaril (VP-63843) 3-[3,5-dimethyl-4[[3-(3-methyl-5-isoxazolyl)propyl] oly]phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole is a novel, broad spectrum antipicornaviral agent. Pleconaril binds to a hydrophobic pocket in the viral capsid inducing conformational changes, which lead to altered receptor binding and viral uncoating. Pleconaril is orally bioavailable and achieves serum concentrations in excess of those required to inhibit 90% of clinical rhino- and enteroviral isolates in vitro. It possesses the additional advantage of achieving several fold higher concentrations within the central nervous system and nasal secretions than in serum, a characteristic that is highly desirable for an antiviral targeted towards viruses known to cause central nervous system and upper respiratory tract infections. Approximately 80% of an orally administered dose is excreted in the faeces within 48 h. Urine excretion accounts for the remainder of the drug. Pleconaril has demonstrated an excellent safety profile in dose escalation and clinical studies. Clinical studies have reported a reduction in the duration and intensity of symptoms in children and adults with enteroviral meningitis and in adults with rhinoviral respiratory tract infections treated with pleconaril. Lastly, pleconaril has demonstrated efficacy in the treatment of severe life-threatening enteroviral infections of the newborn and in immunosuppressed individuals. Pleconaril appears to be a promising drug for the treatment of enteroviral and rhinoviral infections.
Romero
J R
JR
Combined Division of Pediatric Infectious Diseases, University of Nebraska Medical Center and Creighton University, Omaha NE 68178, USA. jrromero@creighton.edu
D000998:Antiviral Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004769:Enterovirus Infections / Q000188:drug therapy*; D006801:Humans; D010069:Oxadiazoles / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010080:Oxazoles
D000998:Antiviral Agents; D010069:Oxadiazoles; D010080:Oxazoles; C115201:pleconaril