BackgroundFusobacterium 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. MethodThe 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 ResultThe 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 ConclusionThe ligands show promising drug-like potential that can be exploited further towards an alternative medication for managing F. nucleatum subgingival dental oral diseases.