In silico and in vitro Study on the Inhibition of FtsZ Protein of Staphylococcus aureus by Active Compounds from Andrographis paniculata

Abstract Both organ systems, ranging from isolated skin infections to life-threatening systemic infections are implicated in the gram-positive bacterium Staphylococcus aureus, responsible for a wide range of human diseases. Filamentous temperature-sensitive protein Z (FtsZ) is a protein encoded by the FtsZ gene that assembles into a Z-ring at the potential site of the septum of bacterial cell division. Structurally, FtsZ is a eukaryotic tubulin homolog that has a low resemblance in sequence; that makes it possible to acquire FtsZ inhibitors without impacting the division of eukaryotic cells. Hence, in our research, we tried to test compounds from the Andrographis paniculata plant using molecular docking and dynamic simulations as an efficient inhibitor of the S. aureus FtsZ protein. We have picked Andrographolide, Neoandrographolide, Andrograpanin, and 14-deoxyandrographolide as the best inhibitor for the FtsZ protein based on the docking results. In terms of docking score and hydrogen bond interaction, Andrographolide exhibited very good results relative to all other compounds. So the docked Andrographolide-FtsZ protein complex has been further analysed through simulation of molecular dynamics. Results of MD simulations indicate that the compound was excellent at linking the target protein and preserving firm connexions throughout the protein backbone structures, creating very little negligible disruption. Finally, the in vitro antimicrobial activity findings of these four compounds also showed that selected compounds may serve as a potent S.aureus inhibitor.