Identification of New Marine‐Based Inhibitors Against Tetracycline Destructase in <i>Acinetobacter baumannii</i> 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 destructase (TDase), which compromises the efficacy of tetracyclines. Consequently, there is a pressing need to discover novel molecules capable of inhibiting TDase activity and thereby enhancing the drug's potency. In this study, we identify novel inhibitors for 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 behavior of TDase through molecular simulations. These findings hold promise for the development of novel and efficacious therapeutics against bacterial infections.