Structural insights of Quercetin and its derivatives against multi-drug resistant Proteus mirabilis: In silico approach

Aims This study aims to explore natural compounds as potential inhibitors against multidrug-resistant Proteus mirabilis hemolysin, a key virulence factor contributing to catheter-associated urinary tract infections (CAUTIs). The emergence of multidrug-resistant bacterial strains poses a significant threat to global public health, with Proteus mirabilis being a notable contributor to hospital-acquired infections such as CAUTIs. Hemolysin, a toxin produced by P. mirabilis , plays a crucial role in its pathogenesis, making it an attractive target for antimicrobial therapy. The objective of this study is to investigate the binding affinity and stability of natural compounds, particularly derivatives of quercetin, with P. mirabilis hemolysin through molecular docking and dynamics simulations. Crystal structure retrieval of hemolysin from P. mirabilis was conducted, and the protein was prepared for molecular docking studies. Molecular docking analysis was performed to evaluate the binding affinity of natural compounds with hemolysin. Molecular dynamics simulations were then employed to assess the stability and dynamics of protein-ligand complexes. Molecular docking analysis revealed several lead compounds, including derivatives of quercetin, exhibiting strong binding affinity with P. mirabilis hemolysin. Molecular dynamics simulations demonstrated stable interactions between the lead compounds and hemolysin, with certain compounds showing reduced structural deviations and increased stability within the binding cavity. Natural compounds, particularly derivatives of quercetin, show promising antimicrobial activity against multidrug-resistant Proteus mirabilis hemolysin. These findings highlight the potential of natural compounds as effective inhibitors for combating multidrug-resistant bacterial infections, offering new avenues for therapeutic development in the fight against antibiotic resistance. Further research and clinical trials are warranted to validate the efficacy and safety of these compounds for clinical use.