## 2 Results
### Unknown or Other Mechanisms of Action
#### 2.4.1 Anti-Rhinovirus  
In the 1950s, some anti-rhinovirus were developed without identifying the viral part targeted and evaluated in clinical trials (Table 4) to assess their efficacy, as represented in Figure 4. Clinical trials were performed using nasally administered rhinoviruses. Figure 4: Structure of anti-rhinoviral compounds, which were evaluated in clinical trials. Chemical groups and atoms in purple are chemical functions that can lead to the fusion or the attachment of a linker to form an MTDL. \begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline \multirow{2}{*}{**Publication Date**} & \multirow{2}{*}{**Type of Study \({}^{*}\)**} & \multirow{2}{*}{**Virus/Disease**} & \multicolumn{2}{c}{**Type of Infection (Time to**} & \multicolumn{1}{c}{**} & \multicolumn{1}{c}{**} & \multicolumn{1}{c}{**} & \multicolumn{1}{c}{**} \\  & & & **Treatment Interval \(\cdot\)** & **Drug** & **Pharmaceutical Form** & **Patient Age** & **Ref.** \\ \hline \hline
19 Jy 1976 & Rdm ID PC Phase II & RV-B3 & Incalculate \((-1.4\,\mathrm{day})\) & SKP 4991, CR-B388, RF 19326 & Solution spray/supersonic drop & 18-50 years old & [79] \\ October 1984 & Rdm ID PC Phase II & RV-A9 & Incalculate \((-1.4\,\mathrm{day})\) & R00 \((-1.4\,\mathrm{day})\) & Oral capsule & 18-50 years old & [80] \\ May 1985 & Rdm ID PC Phase II & RV-E1, RV-B1 & Incalculate \((-1.4\,\mathrm{day})\) & 44 \((018\,\mathrm{R})\) & Nasal spray & 18-50 years old & [81] \\ December 1986 & DC Phase II & RV-A2 & Incalculate & R00 \((0.91\,\mathrm{m})\) & Nasal spray & 18-50 years old & [82] \\ July 1990 & Phase II & RV-A2 & Incalculate & R00 \((0.94\,\mathrm{m})\) & DMSO solution & 18-50 years old & [83] \\
13 May 2022 & Rdm ID PC Phase I & Asthma with RV & Incalculate & CRS3723868 & Inhabiation powder & 18-50 years old & [84] \\
26 May 2022 & Rdm ID PC Phase I & COPD with RV & Incalculate & CRS3723868 & Inhabiation powder & 18-45 years old & [85] \\ \hline \end{tabular} \({}^{*}\)Rdm = randomized, DB = double-blind PC = placebo-controlled \({}^{*}\) Negative delay means that the treatment began before the virus challenge or symptoms onset.  
\end{table} 
Table 4: Summary of clinical assays of drugs with unknown mechanism of action against Rhinoviruses. [PERSON] (RP) studies  
Rhone Poulenc was one of the first laboratories to synthesize some anti-rhinoviral candidates evaluated in clinical trials. In 1976, a randomized, double-blind, placebo-controlled phase 2 clinical trial was published to evaluate the efficacy of SKF 40491 (Smith Kline and French Laboratories, Philadelphia, PA, USA), GL R9-338 (Glaxo Laboratories, Greenford, England), and RP 19326 (Rhone Poulenc, Vitry-sur-Seine, France) against RV infections [79]. The treatment began 1 day before the virus challenge. As a solution spray or a suspension drop, these compounds were delivered to 89 patients with one dose of 1, 6.8, and 15 mg per day respectively. Unfortunately, the in vivo half-time of these drugs was too short to observe striking clinical improvement. [PERSON] conducted another randomized placebo-controlled phase 2 clinical trial in 1987 to evaluate the effect of 44 081 R.P. (Rhone Poulenc, Vitry-sur-Seine, France) against inoculated RV-EL and RV-1B infections [81]. The treatment began 1 day before the virus challenge. A total of 58 patients were recruited to receive 300 \(\upmu\)g of the drug or placebo six times daily for 6 days. Again, no significant efficacy was observed against RV infections. * Roche (Ro) studies  
Roche also performed three phase 2 clinical trials to measure the efficacy of one different compound each time against RV infections. In 1984, the first randomized, double-blind, placebo-controlled study was published to evaluate the effect of Ro 09-0415 (Nippon Roche KK, Kamakura, Japan) against inoculated RV-A9 infections [80]. The treatment began 15 h before the virus challenge. The drug was delivered as an oral capsule, containing 100 mg of the drug, twice daily, for 6 days, to a part of 57 patients.