Pleconaril, a Novel Antipicornaviral Agent

Naomi R. Florea, Pharm.D., Dana Maglio, Pharm.D., David P. Nicolau, Pharm.D., FCCP

Disclosures

Pharmacotherapy. 2003;23(3) 

In This Article

Treatment

Treatment of the picornaviruses is primarily symptomatic. While science tries to find new therapeutic modalities, patients have to rely on remedies targeted not to the virus, but to symptoms. Such treatments include first-generation antihistamines and nonsteroidal antiinflammatory drugs. Other potential treatments are ipratropium bromide, oral and topical decongestants, antitussives, vitamin C, zinc, and echinacea.

Despite symptomatic therapy, no specific agents are available to treat or prevent enterovirus and rhinovirus diseases. However, characterization of the three-dimensional structure of picornaviruses has allowed development of compounds targeted at the virus itself. On the surface of the virus capsid is a hydrophobic pocket. This pocket is associated with a pore in the canyon floor that accesses a channel leading to the interior of the virus and is believed to have an important role in the virion-uncoating process.[8] The canyon floor is the presumed binding site for ICAM-1 located on epithelial cells. Agents designed to bind to the hydrophobic pocket, known as capsid-binding agents, increase conformational stability of the capsid and thus prevent uncoating of the virus once it enters the intracellular space. Virion uncoating is essential to the life cycle of the virus.

Several capsid-binding agents were developed but did not show promising results clinically. Issues such as complex drug metabolism or lack of broad-spectrum antipicornaviral activity halted their development. Pleconaril (ViroPharma Inc, Exton, PA), a novel, orally available, systemic-acting small molecule synthesized in 1991, has antipicornavirus activity and is in clinical trials for treatment of viral respiratory infections.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....