Identification of Novel Marine-based Inhibitors against Tetracycline Destructase in Acinetobacter Baumannii using Computational Approaches

Abstract Tetracyclines are indispensable antibiotics employed to treat a broad spectrum of bacterial infections. However, the emergence of clinical pathogens exhibiting significant resistance to these drugs has posed a formidable challenge in managing bacterial diseases effectively. This resistance is attributed to the proliferation and diversity of resistance genes and various mechanisms that render tetracyclines inactive. A prevalent mechanism of resistance is enzymatic inactivation by tetracycline destructases, which compromises the efficacy of tetracyclines. Consequently, there is a pressing need to discover novel molecules capable of inhibiting tetracycline destructases activity and thereby enhancing the drug’s potency. In this study, we identify novel inhibitors for tetracycline destructase (TDase) in Acinetobacter Baumannii , utilizing compounds derived from marine environments. Through a high-throughput virtual screening approach, we have investigated the potent natural marine compounds interaction and dynamic behaviour of tetracycline destructase through molecular simulations. These findings hold promise for the development of novel and efficacious therapeutics against bacterial infections.