In-silico assessment of bioactive compounds from chewing stick (Salvadora persica) against N-acetylneuraminate lyase (5ZKA) of Fusobacterium nucleatum involved in salicyclic acid metabolism

Fusobacterium nucleatum is implicated in the formation of subgingival dental plaques. The main therapy of choice is the use of non-surgical periodontal therapy; however, this has been shown to be unable to remove Fusobacterium nucleatum completely informing the need for an alternative therapy. The aim of this study was to evaluate in-silico, the mechanism with which bioactive compounds from Chewing stick (Salvadora persica) mediate their action against F. nucleatum. The bioactive compounds 5-Hydroxymethylfurfural (PubChem CID: 237332), furan-2-carboxylic acid, 3-methyl-, trimethylsilyl ester (PubChem CID: 587050), and d-Erythro-Pentofuranose, 2-deoxy-1,3,5-tris-O-(trimethylsilyl) (PubChem CID: 525316) from S. persica and target protein N-acetylneuraminate lyase (5ZKA) were retrieved from literature and protein database, prepared and utilised for docking and molecular simulations using standard protocols with metronidazole and co-crystal as controls. In addition, the pharmacokinetic (ADMET) properties and density functional theory (DFT) were also evaluated The docking scores were -6.7 for the control co-crystal, -5.6 for metronidazole, -5.5 for 5-Hydroxymethylfurfural, -5.2 for d-Erythro-Pentofuranose, 2-deoxy-1,3,5-tris-O-(trimethylsilyl)- and -5.9 for furan-2-carboxylic acid, 3-methyl-, trimethylsilyl ester. Molecular simulation indicate RMSD and RMSF values suggestive of stable complexes during most of the simulation runs, especially so for 5-Hydroxymethylfurfural and Furan-2-carboxylic acid-3-methyl- trimethylsilyl ester that returned RMSD values less than 1.8 Å and RMSF values that were generally less than 2.0. Our ADMET prediction indicates that the test ligands had better pharmacokinetic than the standard drug except for furan-2-carboxylic acid and d-Erythro-Pentofuranose, 2-deoxy-1,3,5-tris-O- that showed hepatotoxicity. In addition, our DFT result indicated that the reactivity of the ligands were slightly less than that of metronidazole The ligands show promising drug-like potential that can be exploited further towards an alternative medication for managing F. nucleatum subgingival dental oral diseases.