Identification of Novel and Safe Fungicidal Molecules against Fusarium oxysporum from Plant Essential Oils: In Vitro and Computational Approaches.

Phytopathogenic fungi are serious threats in the agriculture sector especially in fruit and vegetable production. The use of plant essential oil as antifungal agents has been in practice from many years. Plant essential oils (PEOs) of Cuminum cyminum , Trachyspermum ammi , Azadirachta indica , Syzygium aromaticum , Moringa oleifera , Mentha spicata , Eucalyptus grandis , Allium sativum , and Citrus sinensis were tested against Fusarium oxysporum . Three phase trials consist of lab testing (MIC and MFC), field testing (seed treatment and foliar spray), and computer-aided fungicide design (CAFD). Two concentrations (25 and 50  μ l/ml) have been used to asses MIC while MFC was assessed at four concentrations (25, 50, 75, and 100  μ l/ml). C. sinensis showed the largest inhibition zone (47.5 and 46.3 m 2 ) for both concentrations. The lowest disease incidence and disease severity were recorded in treatments with C. sinensis PEO . Citrus sinensis that qualified in laboratory and field trials was selected for CAFD. The chemical compounds of C. sinensis PEO were docked with polyketide synthase beta-ketoacyl synthase domain of F. oxysporum by AutoDock Vina. The best docked complex was formed by nootkatone with -6.0 kcal/mol binding affinity. Pharmacophore of the top seven C. sinensis PEO compounds was used for merged pharmacophore generation. The best pharmacophore model with 0.8492 score was screened against the CMNP database. Top hit compounds from screening were selected and docked with polyketide synthase beta-ketoacyl synthase domain. Four compounds with the highest binding affinity and hydrogen bonding were selected for confirmation of lead molecule by doing MD simulation. The polyketide synthase-CMNPD24498 showed the highest stability throughout 80 ns run of MD simulation. CMNPD24498 (FW054-1) from Verrucosispora was selected as the lead compound against F. oxysporum .