Nathar_2025_Mol.Divers__

Nocardiosis can lead to disseminated disease and affect various physiological systems, most commonly the skin, lungs, and central nervous system. Nocardia farcinica is unique among other Nocardia species due to its high pathogenicity and antibiotic resistance, and it is more likely to cause brain abscesses and other widespread infections affecting multiple organs. Therefore, new treatment targets are urgently needed to combat the multidrug-resistant nosocomial pathogen N. farcinica. This study aims to prioritize candidate inhibitors using structural bioinformatics and identify prospective therapeutic targets involved in the distinct metabolic pathways of N. farcinica, along with high-throughput virtual screening to identify potential drug compounds. The alpha/beta hydrolase fold domain-containing protein has been identified as a promising target for therapeutic development. Virtual screening of the CMNPD, MNPD, Seaweed, and Specs chemical libraries identified five promising candidates based on their ADME properties and binding affinities. Among these, MNPD738 was inferred as a potent inhibitor due to its stability throughout the molecular dynamics simulation and low binding free energy. These putative therapeutic targets will aid in the development of effective drugs that inhibit the metabolic pathways unique to pathogens. The identified drug targets and lead compounds may contribute to the development of effective therapies for combating drug-resistant N. farcinica infections. Future research should focus on experimental validation of the identified compounds and further exploration of the mechanism underlying N. farcinica pathogenicity.