A Computational Approach to Repurposing Natural Products for DprE1 Inhibition

Abstract

This study aimed to investigate the potential of natural products (NPs) as inhibitors of decaprenylphosphoryl-D-ribose 2′-epimerase (DprE1), an enzyme crucial in Mycobacterium tuberculosis cell wall synthesis. Over 100 NPs were screened for anti-TB properties. Subsequently, the binding mechanism of the most potent inhibitor to DprE1 was investigated using computational methods, including molecular docking and simulations. Three compounds (CNP0123918, CNP0041612, and CNP0281145) were identified with promising binding interactions within DprE1’s active site. CNP0123918 emerged as the top candidate, exhibiting good interaction with key residues in DprE1. This study suggests that computer-aided drug repurposing holds potential as a successful strategy for identifying novel anti-TB drugs. These findings contribute to the development of novel DprE1 inhibitors. Future research will focus on in vitro assays and in vivo and toxicology assessment of CNP0123908 to establish its potential as an effective DprE1 inhibitor.