Porphyromonas gingivalis is the conductor of the orchestration of periodontium inflammation.
Considering that a wide range of antibiotics have lost their activities
in the last century, this study aimed to introduce novel and
broad-spectrum drug targets against this pathogen. For this purpose, the
core proteins of 17 P. gingivalis strains
were obtained. Out of 1418 core proteins, 166 cytoplasmic, essential
factors with no sequence similarity to host were selected. Fifty-two P. gingivalis metabolome-specific
proteins were detected and then 31 novel drug targets were identified
using the DrugBank database. Finally, nine broad-spectrum, novel drug
targets were introduced. Acetate kinase (Ack) was selected as a novel target for drug discovery procedure due to the crucial role of this protein in the survival of P. gingivalis.
Subsequently, structure-based virtual screening revealed six lead
compounds with the most desirable features. Neoagarohexaose,
Lucensomycin, Tetrafibricin, Naquihexcin_H, Tetramycin_A, and
Platensimycin_D. Interestingly, Platensimycin_D1 had highest
drug-likeness features in comparison to other lead compounds. While,
Tetramycin_A and Lucensomycin showed better ADMET properties. The hit
compounds identified here would be an initial compounds for experimental
susceptibility testing against this pathogen. In addition, these
findings might help out with the future studies on development of new
therapeutic agents against P. gingivalis.