Assessment of <i>Melia azedarach</i> Plant Extracts Activity Against Hypothetical Protein of <i>Mycobacterium tuberculosis</i> via GC-MS Analysis and <i>In Silico</i> Approaches

Medicinal plants have played an important role in treating different diseases. Melia azedarach is a plant with significant medical and biological applications. This research aimed to explore the possible bioactivity of various biological compounds. The gas chromatography-mass spectrometry (GC-MS) analysis of Melia azedarach identified 25 compounds, among which 1-ethyl-3-methyl-2-nitrosobenzene and 2-ethyl-1,3-dimethyl-5-(nitromethyl)benzene were the main phytochemicals present in the crude extract of Melia azedarach. Mycobacterium tuberculosis is a zoonotic pathogen that causes tuberculosis (TB). The hypothetical protein OHO21363.1 of Mycobacterium tuberculosis is characterized using an in silico approach for exploring immunogenicity and virulence. After the homology prediction and characterization, this protein was predicted to be a PEE family protein with virulence and immune response functions. This virulent protein lies in the extracellular region of the cell according to subcellular localization and gene ontology. Due to its virulence factor and disease privilege against the host immune response, it can be used as a potential receptor for drug designing. After the GC-MS analysis, the 28 phytochemicals were retrieved and analyzed. Pharmacophore characterization of 1-ethyl-3-methyl-2-nitrosobenzene and 2-ethyl-1,3-dimethyl-5-(nitromethyl)benzene was performed to get the initial information on phytochemical bonding properties. Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) predicted that out of 28 drugs, only 2 could cross the PGP+ through the blood–brain barrier and gastrointestinal tract without violating Lipinski’s rule of 5. Both 1-ethyl-3-methyl-2-nitrosobenzene and 2-ethyl-1,3-dimethyl-5-(nitromethyl) benzene were predicted to have the best docking score against the protein, with –4.9 KJ/Mol and –5.0 KJ/Mol, respectively. Molecular dynamics simulation showed favorable results and provided useful information about the behavior and interactions of the molecules in the dock complex. Immune simulation confirms no immune response on the protein, proving it to be a virulent protein. The phytoconstituents present in Melia azedarach have the potential for multiple pharmacological applications. These findings can be used to design the potential drug candidates against TB. These ligands may be good candidates to fight against the resistant strain of TB compared to the drugs available in the market in the future. More research must be conducted to identify the bioactive compounds that may be used to treat different ailments.