Antifungal plant flavonoids identified in silico with potential to control rice blast disease caused by Magnaporthe oryzae

Abstract

Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae’s infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions.

Identification of plant based potential antifungal compounds against BMK-1 protein of Bipolaris oryzae using molecular docking approach

“…Advanced bioinformatics tools have made it easier to predict the binding affinity of bioactive compounds for proteins that are important for pathogen infection. These tools have successfully been employed for in silico identification of potential phyto-fungicide candidates against Magnaporthe oryzae , a rice blast pathogen 55 . To identify the inhibitory molecules against Big Mitogen Activated Proteinase Kinase-1 (BMK-1) of B. oryzae , which is an important enzyme related to growth, conidiation and pathogenicity, five compounds (chlorogenic acid, eugenol, gallic acid, quercetin, and ursolic acid) from clove were selected for molecular docking based on their antimicrobial activity, as mentioned in the literature.…”