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.

Magnaporthe oryzae是最臭名昭著的真菌病原体之一，可引起谷物稻瘟病，并导致谷物产量的巨大损失。许多化学杀菌剂被用来控制病原体，但没有一种能完全有效地控制稻瘟病。因此，需要发现一种新的天然生物杀真菌剂来有效地防治稻瘟病。大量新天然产物显示出对米霉的抑制活性体外。为了找出有效的生物杀真菌剂，我们对一些针对四种酶的强效天然化合物进行了计算机分子对接分析，这四种酶分别是：sccytalone 脱水酶、SDH1 (PDB ID:1STD)、三羟基萘还原酶、3HNR (PDB ID:1YBV)、海藻糖-6 -调节黑色素生物合成和/或附着细胞形成的米支原体真菌的磷酸合酶 Tps1 (PDB ID:6JBI) 和异柠檬酸裂解酶 ICL1 (PDB ID:5E9G) 。先前报道的 39 种天然化合物可抑制M. oryzae的生长对上述酶进行刚性和柔性分子对接，然后进行分子动力学模拟。虚拟筛选的结果表明，与参考商业杀菌剂嘧菌酯和嗜球果伞素相比，在 39 种化合物中，有八种化合物与任何一种目标酶显示出良好的结合能。在这些化合物中，喜树碱、GKK1032A2 和 chaetoviridin-A 与M. oryzae的一种以上靶酶结合。除三环唑外，所有化合物均显示出良好的生物活性评分。总之，我们的结果表明所有八种化合物都有开发新杀菌剂的潜力，并且值得注意的是，喜树碱、GKK1032A2 和毛壳素-A 可以作为多位点作用模式杀菌剂对抗稻瘟病真菌。