In Silico Evaluation of Human Cathelicidin LL-37 as a Novel Therapeutic Inhibitor of Panton-Valentine Leukocidin Toxin of Methicillin-Resistant Staphylococcus aureus .

Incidence of drug resistance in clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) is attributed to its diverse repertoire of virulence factors. Of these virulence determinants, Panton-Valentine Leukocidin (PVL) has been experimentally validated as a prospective drug target due to its conspicuous and comprehensive role in nosocomial infections. This study encompassed an in silico approach to elucidate the antimicrobial potentiality of human cathelicidin LL-37 against PVL toxin of MRSA. Molecular docking studies of LL-37 and its segments with the PVL toxin subunits LukS and LukF were carried out using PatchDock server and the results were refined using FireDock server. The paramount ligand-receptor combination was selected and analyzed based on diverse parametric attributes and compared with the commercial inhibitors of PVL viz. Andrimid, Beclobrate, Beta-sitosterol, Diathymosulfone, and Probucol to determine the most potent inhibitor among them. Our results elucidated that the interaction of LL-37 with the LukS subunit of PVL toxin (minimum global energy of -61.82 kcal/mol) depicted 34 molecular interactions, while the commercial PVL inhibitors depicted fewer and insubstantial interactions. SWISS-ADME (Absorption, Distribution, Metabolism, and Excretion) and ToxinPred analysis of LL-37 further corroborated its null potency of toxicity in systemic milieu. The results obtained may credit this study as basis for the development of LL-37 as a potential inhibitor against virulent MRSA toxins, thereby exalting the treatment regimes for nosocomial infections in health care facilities worldwide.