Potential inhibitors of PspA receptor against Streptococcus pneumoniae using molecular docking and network pharmacology

Abstract

Background: Streptococcus pneumoniae, or pneumococcus, is a Gram-positive bacterium prevalent in the human respiratory tract, capable of causing a spectrum of illnesses, from mild respiratory infections to severe diseases like pneumonia and meningitis. Its diverse serotypes pose a global health threat, emphasizing the importance of ongoing research to unravel molecular interactions and develop targeted interventions, including vaccines and antibiotics. The study aims to uncover the molecular interactions between the PspA receptor and various ligand inhibitors, employing comprehensive protein and ligand preparation, molecular docking simulations, network pharmacology analyses, and protein-protein interaction networks to identify potential therapeutic pathways and novel treatment options.
Methods: The study employed the pneumococcal surface protein A (PspA) receptor complex and potential ligand inhibitors. Utilizing PyRx Tools for molecular docking simulations, protein and ligand structures were prepared followed by interaction analysis using PyRx and 3D visualization with PyMOL. Network pharmacology and protein-protein interaction networks were explored, employing STITCH and ShinyGO 0.77 web servers, respectively, to predict therapeutic pathways and potential treatment options associated with the identified compounds.
Results: Norlichexanthone exhibited the highest binding affinity to the PspA receptor among the studied compounds. Visualization techniques provided detailed insights into hydrogen bonding patterns with norlichexanthone, ceftriaxon, and NAG. 3D images and network representations enriched our understanding of spatial and network interactions involving the PspA receptor and bioactive components from marine sponges.
Conclusion: This research, combining computational tools, validation procedures, and advanced visual representations, yields valuable insights into the potential of norlichexanthone as a lead compound for further development in addressing Streptococcus pneumoniae infections. The study's findings contribute to the broader field of infectious disease therapeutics, emphasizing the significance of natural products in drug discovery.