CHARLOTTESVILLE, VA—In a phase III trial, the antiviral agent pleconaril both attenuated rhinoviral symptoms and shortened the duration of those symptoms by approximately one day.[1] With no reported severe adverse reactions, the oral medication could potentially alleviate the suffering of many cold victims and may also lessen their likelihood of transmitting rhinoviruses to others.

“The effects we’re seeing are a reduction in duration and severity. Significant reductions in cold symptoms were seen within two days of initiation of pleconaril,” Frederick G. Hayden, MD, told PULMONARY REVIEWS. “Importantly, there were already reductions in symptoms within 24 hours. There was also a reduction in duration of one day in a seven-day illness,” said Dr. Hayden, Professor of Internal Medicine and Pathology at the University of Virginia.

PLECONARIL HASTENS RECOVERY FROM COLDS

In the study, 1,044 otherwise-healthy adult patients presenting with moderate rhinorrhea and at least one other respiratory symptom within the preceding 24 hours were randomized to receive 400 mg oral pleconaril or placebo three times daily. “We took nasal mucus cultures on days 3 and 6,” said Dr. Hayden. “Overall, about two thirds of the individuals had a cultivable picornavirus.”

Pleconaril treatment significantly reduced viral RNA titers in samples cultured on days 3 and 6 of the study. Furthermore, among patients initially testing positive for picornavirus, the primary outcome—complete resolution of rhinorrhea, with other symptoms nearly absent—occurred in pleconaril-treated patients 1.5 days sooner than in the placebo recipients (median, 6.2 vs 7.7 days). Drug treatment also produced a markedly greater reduction in symptom severity within 12 to 24 hours after initiation (20.7%, vs 11.1% with placebo). Furthermore, it significantly lowered mucus production and use of cold medications (by 25% and 21%, respectively, relative to controls).

No adverse reactions were noted during the study. Although the researchers detected a slight elevation in serum cholesterol levels, said Dr. Hayden, “First, I’d ask, ‘Is it real?’ and second, it’s probably clinically insignificant and reversible,” as the drug would not be taken long-term.

PLECONARIL BLOCKS PICORNAVIRAL INFECTIVITY

“In laboratory studies, pleconaril is active only against picornaviruses, such as enteroviruses and rhinoviruses,” said Dr. Hayden. More than half of all viral respiratory infections are caused by picornaviruses. “Pleconaril is not active against all, but it inhibits about 90% of all picornaviruses,” he noted. “It is a viral capsid-binding agent, which binds to a hydrophobic pocket within the protein shell of a picornavirus. Attachment to ICAM-1 [intercellular adhesion molecule 1] is impaired, and impairment of flexibility of the capsid protein interferes with viral uncoating, which is required for host cell infection,” he explained.

Other studies have shown that pleconaril may have protective efficacy against experimentally induced colds. Although pleconaril has not yet been approved by the Food and Drug Administration for any indication, it might be considered for use against other picornaviral infections, said Dr. Hayden. “There have been some interesting preliminary results with enteroviral meningitis,” for which compassionate use of pleconaril has been allowed, he noted.

—Mimi Zucker, PhD

Reference
1. Hayden FG, Kim K, Hudson S. Pleconaril treatment reduces duration and severity of viral respiratory infection (common cold) due to picornaviruses. Presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy, a meeting of the American Society for Microbiology; December 17, 2001; Chicago, Ill. Presentation 659.

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