Structure-based inhibition of Rhizoctonia solani in rice sheath blight Beta-glucosidase by natural terpenoids

Abstract

Rice, a primary staple crop, is highly susceptible to fungal pathogens, with Rhizoctonia solani induced sheath blight being one of the most economically significant diseases, leading to substantial yield losses. The widespread leaning on synthetic fungicides has resulted in resistance development, environmental toxicity, and non-target effects, necessitating alternative eco-compatible disease management strategies. Natural terpenoids, with their broad-spectrum antifungal properties, present a promising biocontrol approach against R. solani. In this study, an in silico structure-based drug design approach was employed to target Beta-glucosidase, a key cell-wall degrading enzyme in R. solani. Due to the unavailability of its experimentally resolved 3D structure (Uniprot ID: A0A8H7H8J1), homology modelling was performed using SWISSMODEL, MODELLER, MultiFOLD, and AlphaFold2. Structural validation through the SAVES v6.0 server indicated that the MODELLER-derived structure exhibited the highest structural fidelity. A molecular docking study involving 15 major terpenoid constituents of essential oils was conducted, wherein Beta-sitosterol, abietic acid, and palustric acid demonstrated the strongest binding affinities with Beta-glucosidase. Pharmacokinetic evaluation through ADME screening identified palustric acid, a diterpene, as the most stable compound with an optimal partition coefficient. However, ADMET toxicity profiling suggested potential hepatotoxic effects at elevated concentrations, while maintaining an overall favourable environmental safety profile. Given its efficacy and biocompatibility, palustric acid, in conjunction with biocontrol agents and improved agronomic practices, holds potential as an alternative strategy for mitigating R. solani-mediated sheath blight in rice.