## 2 Results
### Structural Proteins
During the second and third studies, there was no significant difference between the placebo and virus-shedding cohorts. Eventually, even if the drug seems to irritate the respiratory mucosa and cause nasal dryness, there is no serious adverse effect, as blood in the mucus case reported on the active cohort. * Pleconaril  
In 1996, two phase 2 clinical trials for the compound WIN 63843 (ViroPharma, Inc., Exton, PA, USA), also named pleconaril or VP 63843, were performed to evaluate its efficacy against CVA21 infections and EV infections, respectively [28; 29]. Pleconaril is a broad-spectrum inhibitor with micro or nanomolar in vitro potency against coxsackieviruses and enteroviruses, except for CVB3 [44]. It was also used to cure echovirus-infected neonates [45]. Respectively, 33 and 38 adults were enrolled to receive a 400 mg total daily dose for 7 days, or 200 mg or 400 mg three times, by the oral route. The first study concluded that pleconaril reduces viral shedding in nasal secretion (\(p<0.001\)), nasal mucus production (\(p=0.004\)), and total respiratory illness symptom scores (\(p=0.013\)) compared with placebo after a virus inoculation. The treatment began 14 h before the virus challenge. However, it also causes some adverse effects, like nausea, abdominal pain, dysmenorrhea, and an increase in the frequency of urine. For the second trial, suspected infected children in the active cohort received three doses of 5.0 mg/kg. No delay between inclusion and treatment is reported. Pleconaril was used as compassionate/last-line treatment. Because of the rarity of EV infections, it was challenging to design a placebo-controlled trial. In 1999, three randomized, double-blind, placebo-controlled studies were performed to evaluate pleconaril efficacy against suspected EV meningitis or sepsis [32; 34; 40]. These studies respectively recruited 20 sepsis suspected patients under 12 months, 250 patients over 14 years old with a white blood cell number concentration superior to 10 mm\({}^{-3}\), and 61 sepsis suspected neonates (with 43 confirmed EV sepsis) patients. Pleconaril was administrated by liquid or suspended oral formulation with respective concentrations of 5 mg/kg/dose (three times a day), 200 or 400 mg (three times a day), and 8.5 mg/kg per day for 7 days. The onset of symptoms had to be, respectively, 36 h, 48 h and 10 days before administration of the first dose of study medication. Conclusions of studies on infants were encouraging with a virus culture which turned to negative quicker for the active cohort (\(p=0.08\)) and a higher survival probability after the treatment (\(p=0.26\)) and over 18 months (\(p=0.07\), \(p=0.23\) for validated enteroviruses infections neonates) even if the duration of hospitalization was similar (\(p=0.18\)). No adverse effects were attributed to the treatment despite the drug's tendency to accumulate. The trial on neonates finished during the study due to the expiration of the study drug. The last study performed on children and adults is more mitigated about its conclusion. Indeed, there are some limitations, such as the low number of patients with validated EV meningitis and the difficulty of oral admission for patients with nausea. The headache resolution is quicker for the active cohort with moderate or severe nausea (\(p=0.009\)) but not for very severe nausea (\(p=0.05\)) or without nausea (\(p=0.15\)). However, there is a light low treatment-related adverse effect (\(p=0.14\)) or treatment-emergent adverse effect (\(p=0.71\)). The analysis is exploratory, not for license, due to a failure to define the clinical benefit of the Food Drug Administration (FDA). In 2000, a randomized, double-blind, placebo-controlled phase 3 of clinical trials was performed on 2096 patients to evaluate pleconaril efficacy against RT-PCR-detected RV common colds [33]. To be included in the study, cold symptoms had to have appeared within 24 h. Patients received 200 mg of oral tablets thrice daily for 5 days. By day 3, there is no culturable virus for pleconaril-treated patients (\(p<0.0001\)).