Exploring Phytochemical Potentials: Molecular Docking Studies for Neutralizing Clostridium perfringens Alpha Toxin

Abstract

Clostridium perfringens biotype A strains producing phospholipase C (Cp-PLC), also called alpha-toxin, is a significant virulence factor contributing to its pathogenicity in humans. CpPLC disrupts the signaling cascade of endothelial cells, platelets, and neutrophils, producing excessive intercellular mediators and adhesion molecules that cause gas gangrene. Although most Clostridium perfringens infections are self-limiting and current medications primarily provide symptomatic relief without complete bacterial eradication, novel therapeutic agents are needed to inhibit severe C. perfringens-related conditions such as gas gangrene effectively. So, we are looking for natural substitutes such as phytochemical flavonoids with excellent antioxidant properties, antibacterial effects, and anti-inflammatory and immunemodulating properties. This research utilizes molecular docking techniques to elucidate potent phytochemicals' binding interactions and affinity by targeting alpha-toxin. In this study, fifteen types of flavonoids (with different chemical conformations) were screened for toxin inhibitors by their bioactive property that obeyed Lipinski’s rule of 5 without any violations. After that, their three-dimensional structure was downloaded from PubChem, Drug Bank, and Zinc Database. This is followed by molecular docking study using AutoDock Vina and Discovery Studio Visualizer to visualize the molecular interactions. The compounds hesperidin, boldione, Curcumin, and Protopine, with the respective binding energy of -12.4, - 12, -9, and -8.7, showed high binding affinity within the catalytic domain of the toxin and prominent interaction with the toxin. The study suggests that these natural compounds can be used as potential lead inhibitors for the alpha toxin