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

Rhinoviruses

Viral respiratory infections have several etiologies ( Table 1 ).[7] During seasonal epidemics, rhinoviruses, with more than 100 serotypes, are implicated in 50-80% of cases of the common cold.[8] Other viruses associated with the common cold are coronaviruses, respiratory syncytial virus, influenza virus, parainfluenza virus, and adenovirus. They can be distinguished from rhinoviruses in that they cause a much smaller proportion of infections, or cause a higher proportion of lower respiratory or systemic symptoms in addition to nasal symptoms characteristic of colds. With the exception of parainfluenza virus, rhinoviruses can further be distinguished from other respiratory viruses by their ability to cause infection throughout the year, with marked peaks in spring and early fall in temperate regions. The epidemiology of other respiratory viruses is characterized by distinct seasonal peaks, with minimal frequency of infection between peaks.[9]

Rhinovirus contains four structural proteins -- VP1, VP2, VP3, and VP4 -- that form a non-enveloped, icosahedral capsid. Deep canyons on the capsid surface contain a receptor-binding domain. The virus evades the host immune system because the capsid surface mutates constantly, although the canyons maintain their antigenic specificity. The canyons are too narrow to accommodate the Fab antibody portion, thereby escaping host deactivation, but are large enough to bind the host cell receptor. The intercellular adhesion receptor molecule-1 (ICAM-1) is the major cellular receptor for 90% of rhinoviruses. This receptor is expressed on nasal epithelial cells, with high concentrations in adenoid sinuses.[10]

The pathogenesis of rhinovirus infections is not completely understood. Most exposures to the virus result in infection in the absence of specific immunity to the infecting serotype. Transmission occurs to some extent through inhalation of aerosolized particles but mostly through hand-nose or hand-eye contact after contamination of the hand with infected secretions. Rhinovirus then invades the host by binding to its cellular receptor, ICAM-1, on nasal epithelial cells. After host cell invasion and replication, the rhinovirus spreads to epithelial cells of the nasal passages to the pharynx and, in some people, may spread to the large airways.[11]

Symptoms of the common cold are generally mild to moderate in healthy individuals. They usually begin 1-2 days after infection, with peak symptoms occurring after 2-4 days. Early symptoms include nasal obstruction, rhinorrhea, sneezing, and sore or scratchy throat. Cough is present in approximately 30% of colds and is reported to be the most bothersome and persistent symptom later in the disease course.[12] Most rhinovirus colds last 1 week, but approximately 25% last 2 weeks.[2]

In addition to mildly symptomatic colds, rhinovirus infections are associated with a number of upper and lower respiratory tract complications that can have a significant medical impact. Respiratory viruses are important predisposing factors in the development of acute bacterial otitis media, particularly in children. The local edema associated with viral respiratory infections presumably causes obstruction of the eustachian tube, which can lead to the development of acute bacterial otitis media. Rhinovirus has been reported as the most common virus associated with otitis media. Similarly, rhinoviral infection may predispose patients to bacterial sinusitis by entrapping bacteria in the sinus cavity.[13]

Rhinoviruses are increasingly associated with lower respiratory tract illness in adults and children. A study in adults aged 60-90 years reported lower respiratory tract symptoms in 65% of rhinoviral infections. Of those who consulted a doctor, 75% received antibiotic treatment.[14] Evaluation of an outbreak of rhinovirus infection in a long-term care facility demonstrated the capability of the virus to cause severe respiratory illness, especially in patients with underlying lung disease.[15] In infants less than 12 months of age, infection required hospitalization for lower respiratory tract symptoms, especially bronchiolitis, and deterioration in bronchopulmonary dysplasia.[16,17] Rhinoviruses were implicated in exacerbations of asthma in adults and children.[18,19] In patients older than 2 years, they were the most frequently isolated pathogens in asthma exacerbations and hospitalizations.[20] In addition, asthmatic children experience more frequent rhinovirus infections than their siblings, and the infections last longer.[21] Rhinoviruses also are implicated in up to 40% of exacerbations of chronic bronchitis.[22]

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