# Prioritization of Drugs for Fungal Keratitis Eye Infections: An In-Silico Analysis
## 2 Result and Discussion
### Docking Interactions of Anti-Fungal Agents against Aspergillus Fumitigatus  
The best docking interaction score of \(-\)13.7000 kJ/mol was observed for Itraconazole (CID_55283), and is followed by Natamycin (\(-\)12.8050 kJ/mol) and Voriconazole (\(-\)12.6388 kJ/mol), and lastly, by the modeled RNAP from _A. fumigatus_ (Figure 5a-c). The Itraconazole interaction was favored by the formation of Hbond with Ile27 and hydrophobic interactions with Leu21, Leu23, Met24, Cys25, Try26, Ile27, Val29, and Trp166. The lowest dock score of \(-\)6.7883 kJ/mol was exhibited by Econazole (CID_3198), where no Hbonds interactions were observed and non-bonded interactions were favored by Met24, Try26, Trp166, Try177, and Met237. It is evident that, theoretically, all the anti-fungal agents showed better binding with the modeled structure (Table 4) with narrow differences. It was observed that the amino acid Trp1, Val4, and Lys19 in the binding pocket of the modeled DNA dependent RNA polymerase II protein from _A. fumigatus_ played a crucial role in exhibiting Hbond and hydrophobic interactions. The narrow differences in the binding energies of the compounds are attributed to in-vivo and in-vitro inhibition strategies. \begin{table}
\begin{tabular}{c c c c c c c c} \hline
**5281099** & **456201** & **71616** & **55283** & **4189** & **3365** & **3198** & **2812** \\ \hline - & \#Trp1 & \#Trp1* & - & \#Trp1* & \#Trp1* & - & - \\ \hline - & - & Gly2* & - & Gly2* & Gly2* & - & - \\ \hline - & - & - & - & Leu3 & - & - & - \\ \hline \#Val4 & - & \#Val4* & - & \#Val4 & \#Val4* & - & - \\ \hline - & - & \#Cys5 & - & \#Cys5 & \#Cys5 & - & - \\ \hline - & - & \#Pro6 & - & \#Pro6 & \#Pro6 & - & - \\ \hline Glu8* & - & - & - & - & - & - & - \\ \hline \#Lys19 & - & \#Lys19 & - & \#Lys19 & \#Lys19 & - & - \\ \hline \#Asn20 & - & - & - & - & - & - & - \\ \hline \#Leu21* & - & - & \#Leu21 & - & - & - & - \\ \hline - & - & - & \#Leu23 & - & - & - & - \\ \hline - & - & - & \#Met24 & - & - & \#Met24 & - \\ \hline - & - & - & \#Cys25 & - & - & - & - \\ \hline - & - & - & \#Try26 & - & - & \#Try26 & \#Try26 \\ \hline - & - & - & \# Ile27* & - & - & - & - \\ \hline - & - & - & \#Val29 & - & - & - & - \\ \hline - & - & - & \#Trp166 & - & - & \#Trp166 & \#Trp166 \\ \hline - & - & - & - & - & - & \#Try177 & \#Try177 \\ \hline - & \#Ala180 & - & - & - & - & - & - \\ \hline - & \#Glu181 & - & - & - & - & - & - \\ \hline - & \#Glu183 & - & - & - & - & - & - \\ \hline \end{tabular}
\end{table} 
Table 4: Docking interactions of anti-fungal agents within the binding pocket of the modeled DNA dependent RNA polymerase II protein from _Aspergillus fumigatus_. Thus the present docking studies suggest that Itraconazole, followed by the Ketoconazole and Voriconazole, might have significant in-vivo and in-vitro results against \(A\), _flavus_ and \(A\). _fumigatus_. Further, this study implies that the presence of keto groups (=O) on the Itraconazole and amide groups (-N=H) in the binding pocket of amino acids as electro negative elements are crucial for their interactions and for their anti-fungal activity. \begin{table}
\begin{tabular}{c c c c c c c c} \hline
**5281099** & **456201** & **71616** & **55283** & **4189** & **3365** & **3198** & **2812** \\ \hline - & \#Glu184 & - & - & - & - & - & - \\ \hline - & \#Ile188 & - & - & - & - & - & - \\ \hline - & \#Met190 & - & - & - & - & - & - \\ \hline - & - & - & - & - & - & \#Met237 & - \\ \hline - & - & - & - & \#Ile238 & - & & - \\ \hline \#Val241\({}^{\star}\) & - & - & - & - & - & - & - \\ \hline \(-12.8050\) & \(-9.2480\) & \(-12.6388\) & \(-13.7000\) & \(-10.1525\) & \(-11.5391\) & \(-6.7883\) & \(-9.0994\) \\ \hline \end{tabular} \({}^{\star}\) Residues involved in H-bond interactions; #Residues involved in H-bond and non-bonded interactions. #Residues involved in non-bonded interactions. Binding energies (kJ/mol) are provided in the last row.  
\end{table} 
Table 4: _Cont._Figure 5: The docking complex and interactions of the best docked compounds with RNAP from \(A\). _fumigatus_.