The Enterovirus D68 has been in the headlines lately- and not for a positive reason. This rogue virus has parents and practitioners alarmed as it has progressed to severe illness in several children, leading to cases of possible paralysis. Treatment for this virulent strain of the Enterovirus is needed quickly, as some children have experienced not only serious respiratory effects but other children have endured polio like symptoms. New research published at the beginning of January 2015, by experts at Purdue’s Department of Biological Sciences, has pointed to the use of the antiviral compound Pleconaril as a potential therapy to fight this serious illness. As an effective antiviral treatment, Pleconaril not only has proven in R&D to destabilize the virus particle, but it also binds to the “pocket” and inhibits infection. While Pleconaril has not shown to be active against current strains of the Enterovirus D68, it has proven to be a formidable opponent against the original isolate. Future changes anticipated in the structure of Pleconaril through development are surmised to lead to inhibitors which would act against a wider spectrum of isolates.
The summer of 2014 was particularly rough for American children who were affected by the Enterovirus D68, with 1,149 cases confirmed in August. In addition to respiratory symptoms ranging from mild to severe, many children experienced neurological effects such as muscle weakness and paralysis. With no current vaccine or treatment, finding a remedy for this frightening illness is at the forefront of pharmaceutical research. Researchers at Purdue are working with the CDC to study the latest strains of Enterovirus D68 and determine the connection with cases of polio-like symptoms in California children as well. The poliovirus is considered to be an enterovirus and classified in the family of picornaviruses. The majority of enteroviruses, however, are non-polio viruses, and are most like the common cold. These typical enteroviruses cause between ten and fifteen million infections each year in the U.S.
Prior studies of Pleconaril have proven successful for treating picornavirus-associated viral respiratory infections. Phase II trials involved two randomized, multicenter studies of Pleconaril in both adolescents and adults ages 14 and older. These placebo-controlled, double-blind trials saw patients who sought medical care for picornavirus-associated viral respiratory infections at an outpatient facility within 36 hours of infection onset. The patients were diagnosed with moderate to severe respiratory illness that was deemed acute in nature. The first study of the Phase II trials had the patients receiving either Pleconaril 400 milligrams as a liquid form to take orally or a placebo. Pleconaril was dispensed 2 to 3 times a day to affected patients. In the second study patients were administered a 400 milligram Pleconaril tablet to take orally 3 times a day for seven days, or a placebo. Complete resolution of symptoms was the primary endpoint in the first study, with investigators marking the end of the patient’s six major viral symptoms which included nasal congestion, rhinorrhea, sore throat, cough, myalgia and exhaustion. The primary end point in the second study was the amount of time needed until the patient had either mild or absent symptoms for at least 48 hours. The first study demonstrated that treatment with Pleconaril three times daily reduced the time to complete resolution of symptoms by three days as compared to a placebo. The second study found that the time to illness alleviation was sizably shorter in the patient population who received Pleconaril. The safety profile of Pleconaril showed no statistically significant differences in adverse-events as compared to the placebo group. Common side effects from Pleconaril included nausea, stomach pain, diarrhea and headache. The patients who were given the tablet form of Pleconaril fared better than the patients who were administered the liquid form of this drug, as the tablet reduced the frequency of negative gastrointestinal effects.
As a novel, systemically acting molecule with antiviral activity against rhinovirus serotypes Pleconaril is a formidable opponent for the common cold virus. The potential for this potent antiviral medication to be an effectual treatment for the Enterovirus D68 illness is hopeful. LGM Pharma can assist clients as a supplier/distributor of the API Pleconaril CAS# 153168-05-9 for research and development purposes. Clients can be assured of quality API products and continuous support throughout the R&D process.
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