## 2 Results
### Unknown or Other Mechanisms of Action
#### 2.4.2 Broad Spectrum Antiviral  
Numerous rhinovirus inhibitors were developed and studied in clinical trials. However, many other broad-spectrum antivirals have also been evaluated against EV infections (Table 5) and other upper respiratory tract infections caused by viruses. They are represented in Figure 5. \begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline
**Publication Date** & **Type of Study \({}^{\star}\)** & **Virus/Disease** & **Type of Infection (Time to** & **Drug** & **Pharmaceutical Form** & **Patient Age** & **Ref.** \\ \hline March 1973 & DB PC phase II & RV-A9, RV-A13 & Incoulation (\(-1\) day) & Isoprinosine & Oral tablet & 18-50 years old & [87] \\ April 1974 & DB PC phase II & RV-A32, RV-B4 & Incoulation & Isoprinosine & Oral tablet & 25-48 years old & [88] \\ March 1977 & Rdm DC PC phase II & RV-A21 & Incoulation & Isoprinosine & Oral tablet & \textgreater{}18 years old & [89] \\
18 July 2018 & Rdm DC Phase II & EV, RV-A1 & Naturally occurred (+0 h) & Nitzovanide & Oral tablets & \textgreater{}12 years old & [90] \\
13 May 2020 & Rdm DC Phase III & EV, RV & Naturally occurred (+22 h) & Nitzovanide & Oral tablets & \textgreater{}12 years old & [91] \\ May 1970 & Rdm DB PC phase II & RV-A9 & Incoulation (\(-1\) day) & UK2054 & Oral formulation & NS & [92] \\ December 1973 & DB PC phase II & RV-A24 & Incoulation (\(-1\) day) & DQA & Oral capsule & 21-42 years old & [93] \\
14 January 2017 & Rdm DC PC phase II & Upper respiratory & Naturally occurred & ARM-1 & Oral spray & 18-43 years old & [94] \\ \hline \hline \end{tabular}  
* Rdm = randomized, DB = double-blind, PC = placebo-controlled.  
\({}^{\star}\) Negative delay means that the treatment began before the virus challenge or symptoms onset. The positive delay means that the treatment began after the virus challenge or symptoms onset. NS = not specified.  
\end{table} 
Table 5: Summary of clinical assays of broad-spectrum antiviral against Enteroviruses. * Isoprinosine (Inosiplex(r))  
For instance, isoprinosine (Newport Pharmaceuticals, Newport Beach, CA, USA), a combination of inosine, acetamidobenzoic acid, and dimethylaminoisopropanol, has a broad spectrum against several viruses [95]. Three double-blind, placebo-controlled phase 2 clinical trials were published between 1973 and 1977 to evaluate the effect of isoprinosine delivered as an oral tablet against inoculated viruses. The treatment for all trials began 1 day before the virus challenge. The first study targeted RV-A9, and RV-A13 [87]. 55 patients were recruited. They received 6 g daily for 7 days. No significant differences were identified between placebo or drug treatment [96]. In 1974, another clinical trial focused on RV-B30 and RV-B44 infections [88]. A total of 37 males received 1.5 g of the drug or placebo four times. A slight clinical improvement was observed for drug-treated patients, but it was not significant enough to prove the drug's efficacy on these RV serotypes [96]. Finally, a third randomized study was published to evaluate the effect against RV-A21 [89]. A total of 39 patients were recruited to receive oral tablets. In the active cohort, patients received daily 4 g of the drug for 5 or 7 days. This time, significant reductions in clinical illness and viral shedding were observed [96]. Indeed, the active cohort had a lower mean symptom score (\(p=0.04\)) or cumulative symptoms score (\(p<0.001\)). However, no significant difference was identified in mean symptom durations (\(0.05<p<0.1\)). Consequently, isoprinosine is active against RV-A21 and slightly effective against RV-B30 and RV-B44 but not against RV-A9 and RV-A13. No adverse effects caused by the drug were identified. Clinical trials with more patients in cohorts could clarify the efficacy of this drug against RV infections. * Nitzoxanide  
Another actor developed a compound series of broad-spectrum antivirals. In 2018, a randomized, double-blind, placebo-controlled phase 3 clinical trial was performed to evaluate the efficacy of nitazoxanide (Romark Laboratories L.C.)