In Silicoidentification Of Natural Fungicide Frommelia Azedarachagainst Isocitrate Lyase Offusarium Graminearum

Isocitrate Lyase (ICL) is a crucial enzyme involved in the Glyoxylate pathway, essential for the virulence of several fungal pathogens includingFusarium graminearum. ICL is a novel target for the discovery of antifungal compounds andF. graminearumICL inhibitors can be used to control the growth of this fungus. Although, several inhibitors of ICL have been identified, however, most of these inhibitors are not environment-friendly. Hence there is still a need to discover natural inhibitors of ICL that can be more effective. To identify a potential antifungal compound, we performed a structure-based screening of phytochemicals ofMelia azedarachagainst the FgICL structure by molecular docking and 104 ligands were found to have a better docking score as compared to the reference molecule. These compounds were assessed for drug-likeness and ADMET prediction. After molecular docking, drug-likeness and toxicity analysis, six potential compounds (Melianoninol (-6.6 kcal/mol), Nimbinene (-7.7 kcal/mol), Vilasinin (-8.1 kcal/mol), Fraxinellone (-6.7 kcal/mol), Gedunin (-7.8 kcal/mol), and Meldenin (-7.8 kcal/mol)) were subjected for rescoring by X-Score. The structural stability and dynamics of screened compounds at the active site of FgICL were examined using MD simulation and MM-PBSA analysis. The result of MM-PBSA revealed that four phytochemicals viz. Melianoninol, Nimbinene, Vilasinin, and Fraxinellone had binding free energy of -17.25 kcal/mol, -59.35 kcal/mol, -64.79 kcal/mol, and -29.86 kcal/mol, respectively. Molecular dynamics simulation and MM-PBSA demonstrated that these four phytochemicals displayed considerable significant structural and pharmacological properties and could be probable antifungal drug candidates againstF. graminearum.These phyotchemicals ofM. azedarachmay be suitable candidates for further experimental analysis. Communicated by Ramaswamy H. Sarma