In silico molecular docking evaluation reveals high potencies of some natural antifungal metabolites on melanin biosynthesis and appressoria formation enzymes in Magnaporthe oryzae

Abstract 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 effective against blast disease. Thus, there is a demand to discover potential and safe natural biofungicides to manage blast disease successfully. To find out effective biofungicides, we performed in silico molecular docking analysis of some natural compounds targeting four enzymes namely, scytalone dehydratase, SDH1 (1STD), trihydroxynaphthalene reductase, 3HNR (YBV1), trehalose-6-phosphate synthase, Tps1 (6JBI) and isocitrate lyase, ICL1 (5E9G) of M. oryzae fungus that regulate melanin biosynthesis or appresorium formation. Thirty-nine natural compounds that previously reported to inhibit the growth of M. oryzae were subjected to rigid and flexible molecular docking against aforementioned enzymes followed by molecular dynamics simulation and free energy analysis of protein-ligand complexes. The results of virtual screening showed that out of 39, 12 compounds showed good binding energy with any one of the target enzymes as compared to reference molecule azoxystrobin and strobilurin. Among the compounds, camptothecin GKK1032A2 and arohynapene-B bind more than one target enzymes of M. oryzae. All the compounds except tricyclazole showed good bioactivity score. Taken together, our results suggest that all of the 12 compounds have the potential to develop new fungicides but camptothecin, GKK1032A2 and arohynapene could act as multi-site mode of action fungicides against M. oryzae.