Enteroviruses cause 10-15 million symptomatic infections each year in the United States. The common cold is another disease that is caused by rhinoviruses. Both enteroviruses and rhinoviruses are members of the virus family picornaviridae. Viral respiratory infections that are caused by some enteroviruses and rhinoviruses result in a variety of diseases that include viral meningitis, pharyngitis, bronchitis, infectious asthma, pneumonia, and the common cold. However, enteroviruses are responsible for more than 600,000 cases of viral meningitis in the United States each year. Enteroviruses also cause paralytic disease, pericarditis, acute hemorrhagic conjunctivitis, herpangia, and numerous other dangerous diseases. An effective drug is now available that targets these viruses and has the potential to save numerous lives and medical expenses.
Pleconaril is a novel, orally bioavailable drug that is finishing its late-stage clinical trials and will soon be available to the public in treating enteroviral infections. Current results show an impressive decrease in symptoms and time to recovery. The scientists of ViroPharma, the company that produces pleconaril, realized that the picornavirus capsid structure is relatively conserved among the enteroviruses and rhinoviruses. The capsid protein has a hydrophobic pocket that has only subtle differences between enteroviruses and rhinoviruses. By finding the average structure of this pocket through X-ray crystallography, computer modeling, genetic algorithm methodologies, and traditional medicinal chemistry, the scientists of ViroPharma designed a drug that would integrate into the hydrophobic pocket.
Pleconaril has bioavailablity levels nearing 70% and is absorbed well into the blood stream, allowing it to target enteroviral infections. Pleconaril is also able to cross the blood-brain barrier and target the viruses responsible for causing meningitis. Pleconaril is thought to be able to cross the blood-brain barrier because of its lipophilic character. Pleconaril has also been administered to over 1700 people and had no adverse effects besides those also seen in the placebo group. The results of the trials have shown that Pleconaril exhibited antiviral activity against picornaviruses by blocking uncoating of the virus and preventing the release of viral RNA. It has also been shown to prevent viral attachment to human cells.
Pleconaril was shown to have antiviral activity against 214 of 215 enteroviruses and antiviral activity in 95% of all picornaviruses. The effects of pleconaril on enteroviral infections were a two day reduction in duration of headache, allowed patients to return to work two days earlier, and a two reduction in most other symptoms with the clinical benefit being noticed in 24 hours after the initial dose was given. This drug looks very promising and will greatly decrease the number of deaths and severity of illness due to picornaviruses.
Daniel Pevear, Tina Tull, Martin Seipel, and James Groarke. "Activity of Pleconaril against Enteroviruses." Antimicrobial Agents and Chemotherapy. Sept. 1999, Vol 43. No. 9, p. 2109-2115.
John McConnell. "Enteroviruses succumb to new drug." The Lancet. Oct 1999, Vol. 345, p. 1185