RESUMO
Magnaporthe oryzae causes destructive blast disease in more than 50 species of the major cereal crops rice, wheat and maize and destroys food of millions of people worldwide. Application of synthetic chemical fungicides are environmentally hazardous and unreliable in controlling M. oryzae. Conversely, naturally occurring biofungicides with multiple modes of actions are needed to be discovered for combatting the blast fungus. To find the effective biofungicides, we performed molecular docking study of some potential antifungal natural compounds targeting two proteins including a single-stranded DNA binding protein MoSub1 (4AGH), and an effector protein AVR-Pik (5E9G) of M. oryzae that regulates transcription in fungus and/or suppresses the host cell immunity. The thirty-nine natural compounds previously shown to inhibit M. oryzae growth and reproduction were put under molecular docking against these two proteins followed by simulation, free energy, and interaction analysis of protein-ligand complexes. The virtual screening revealed that two alkaloidal metabolites, camptothecin and GKK1032A2 showed excellent binding energy with any of these target proteins compared to reference commercial fungicides, azoxystrobin and strobilurin. Of the detected compounds, GKK1032A2 bound to both target proteins of M. oryzae. Both compounds showed excellent bioactivity scores as compared to the reference fungicides. Results of our computational biological study suggest that both camptothecin and GKK1032A2 are potential fungicides that could also be considered as lead compounds to design novel fungicides against the blast fungus. Furthermore, the GKK1032A2 acted as a multi-site mode of action fungicide against M. oryzae.
RESUMO
Magnaporthe oryzae is one of the most notorious fungal pathogens that causes blast disease in cereals, and results in enormous loss of grain production. Many chemical fungicides are being used to control the pathogen but none of them are fully effective in controlling blast disease. Therefore, there is a demand for the discovery of a new natural biofungicide to manage the blast disease efficiently. A large number of new natural products showed inhibitory activities against M. oryzae in vitro. To find out effective biofungicides, we performed in silico molecular docking analysis of some of the potent natural compounds targeting four enzymes namely, scytalone dehydratase, SDH1 (PDB ID:1STD), trihydroxynaphthalene reductase, 3HNR (PDB ID:1YBV), trehalose-6-phosphate synthase, Tps1 (PDB ID:6JBI) and isocitrate lyase, ICL1 (PDB ID:5E9G) of M. oryzae fungus that regulate melanin biosynthesis and/or appresorium formation. Thirty-nine natural compounds that were previously reported to inhibit the growth of M. oryzae were subjected to rigid and flexible molecular docking against aforementioned enzymes followed by molecular dynamic simulation. The results of virtual screening showed that out of 39, eight compounds showed good binding energy with any one of the target enzymes as compared to reference commercial fungicides, azoxystrobin and strobilurin. Among the compounds, camptothecin, GKK1032A2 and chaetoviridin-A bind with more than one target enzymes of M. oryzae. All of the compounds except tricyclazole showed good bioactivity score. Taken together, our results suggest that all of the eight compounds have the potential to develop new fungicides, and remarkably, camptothecin, GKK1032A2 and chaetoviridin-A could act as multi-site mode of action fungicides against the blast fungus M. oryzae.
