Probing the multitargeted potency of FDA-approved Amifostine against MRSA and control comparison with sulfamethoxazole to establish alternative medications

Abstract

Methicillin-Resistant Staphylococcus aureus (MRSA) is a multidrug-resistant bacterial strain causing infections from mild skin conditions to life-threatening sepsis. It is classified into healthcare-associated (HA-MRSA) and community-associated (CA-MRSA), with significant healthcare and economic burdens. The rising prevalence and resistance to existing antibiotics highlight the urgent need for improved infection control, antibiotic stewardship, and research into multitargeted therapies to combat resistance and ensure effective treatment options. In this study, we performed a multitargeted docking study followed by pose filtering with MM/GBSA of an FDA-approved drug library. We identified Amifostine as a multitargeted inhibitor of transferases and hydrolases proteins involved in MRSA with docking scores ranging from −11.040 to −7.559 kcal/mol. We compared it with Sulfamethoxazole with docking scores −4.851 to −2.868 kcal/mol, which is an approved compound against MRSA, and found Amifostine a far better drug for MRSA instead just for its use to protect the kidneys of patients getting chemotherapy for the treatment of ovarian cancer. We also performed Interaction Fingerprints, pharmacokinetics, 5ns WaterMap and 100ns MD Simulation in water. We compared the results and extended the study with binding free energy and total energy of each MD simulation trajectory computations and found that Amifostine is a far better drug than Sulfamethoxazole—however, experimental validation is needed before its human use.