In silico screening identifies Daphnodorin-C as a potential inhibitor of the PMK1 pathway in the management of rice blast disease

Abstract

Rice blast disease, caused by the fungus Magnaporthe oryzae, is one of the most devastating threats to global food security, especially in nations where rice is staple food. Despite the availability of chemical fungicides, the emergence of resistant fungal strains necessitate the search for alternative, natural and environment friendly solutions. In this study, we utilized in silico screening approaches to identify potential inhibitors targeting the PMK1 pathway, a critical regulator in the appressorium formation and fungal infection. Natural compounds from economically important plants of south Asia available in NPASS database were screened against the target PMK1 protein. In the screening Daphnodorin-C from Daphne odora was identified as a promising candidate, with a docking score of -10.9 kcal/mol. Molecular dynamics simulations (MDS) confirmed the stability of the Daphnodorin-C–PMK1 complex over 100 ns simulation period, with root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) values within permissible limits. Daphnodorin-C exhibited moderate toxicity against T. pyriformis and minnows, suggesting moderate effect on aquatic life if contaminated. It’s in silico safety profile shows no hepatotoxicity or skin sensitization, limited skin permeability, though with mild immune and respiratory effects. These findings suggest that Daphnodorin-C could be a promising lead compound for rice blast disease management.