## 2 Results
### Structural Proteins

Table 1: Summary of clinical assays for VP1 “classical” hydrophobic pocket binders. R61837  
The first clinical trial studying capsid binder as an inhibitor of enterovirus was published in 1989 for a double-blind placebo-controlled phase 2 clinical trial with an evaluation of R61837 (Janssen Pharmaceutical Ltd.) on 105 volunteers between 18 and 50 years old to treat RV-A9 infections [24]. R61837 was prepared for the nasal route, after nasal virus inoculation. The treatment began either 4 or 28 h before the virus challenge. Each patient received a 25 or 36 mg total dose of R61837 daily for 6 days. This trial concluded that R61837 doesn't prevent RV-A9 infections but associated odds. A decrease in nasal secretion and an improvement in the clinical score were observed during the treatment but stopped when patients no longer received the drug. Patients had well-tolerated R61837. The trial conclusion was to increase the drug dose to observe higher efficacy against RV-A9. WIN 54954  
The most famous capsid binder family is derived from drug candidates developed by Winthrop Company (WIN compounds). They possess three aromatic cores with one alkyl linker. In 1990, a second randomized, double-blind, placebo-controlled phase 2 clinical trial was performed to evaluate the efficacy of WIN 54954 against RV-A39 infections [25]. WIN 54954 possessed an in vitro broad-spectrum activity with nanomolar potency against several RV and CV [42]. Two cohorts were recruited in Virginia and South Carolina in January and November 1990. A total of 69 volunteers between 18 and 50 years old were recruited. They were received by nasal route RV-A39. The treatment began 642 h before the virus challenge. WIN 54954 was administrated by oral capsules containing 100 or 400 mg of active ingredient for 6 days for a total dose of 1.20 or 2.40 g per day. The trials concluded that there is no significant efficacy in preventing RV-A39 colds. The main proposed limitations of this study were inadequate daily dose to have sufficient experimental power, lack of performance of measuring instruments, or development of drug resistance during the trial. Pirodavir  
The same year, an R61837 derivative named Pirodavir (R77975) was evaluated for a randomized, double-blind, placebo-controlled phase 2 clinical trial against all RV colds [26]. Pirodavir is an antienteroviral with a nanomolar in vitro potency against a broad spectrum of rhinoviruses and several coxsackieviruses, echoviruses, and enteroviruses [43]. In the first trial, pirodavir was administrated by nasal route. Patients recruited for this study had been suffering from cold symptoms for less than 2 days, and ranged in age from 18 to 64 years. The median treatment time since the onset of illness is 24 h. Every day, patients used the nasal spray twice per nostril for 6 days. Each intranasal spray released 500 ug of drug or placebo diluted at a concentration of 5 g/L. Overall, they received 30 doses of pirodavir. The clinical trial concluded with a non-significant benefit to use the drug with efficacy and some mild adverse effects versus placebo. Indeed, there is a significantly lower frequency of virus isolation on day 3 (\(p<0.001\)) and on day 5 (\(p=0.002\)). However, the active cohort suffered from blood in mucus (\(p<0.01\)), unpleasant taste, and nasal dryness (\(p\leq 0.05\)). A second randomized, double-blind, placebo-controlled phase 2 clinical trial was published in 1992 to evaluate the efficacy of a nasal spray containing pirodavir against inoculated RV-A39 infections [27]. The treatment began 6 or 12 h before the virus challenge. Patients between 18 and 64 years old received two sprays for each nostril per day. They received a total of 2 mg of pirodavir per day. The trial concluded that there is no significant difference in seroconversion rate. However, there is a lower overall number of days of virus shedding on days 2 (\(p<0.001\)), on day 3 (\(p=0.005\)) and day 4 (\(p=0.04\)) for the first study.