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The emergence of drug resistance and the limited number of approved antitubercular drugs prompted identification and development of new antitubercular compounds to cure <i>Tuberculosis</i> (TB). In this work, an attempt was made to identify potential natural compounds that target mycobacterial proteins. Three plant extracts (<i>A. aspera</i>, <i>C. gigantea</i> and <i>C. procera</i>) were investigated. The ethyl acetate fraction of the aerial part of <i>A. aspera</i> and the flower ash of <i>C. gigantea</i> were found to be effective against <i>M. tuberculosis</i> H₃₇Rv. Furthermore, the GC-MS analysis of the plant fractions confirmed the presence of active compounds in the extracts. The <i>Mycobacterium</i> target proteins, i.e., available PDB dataset proteins and proteins classified in virulence, detoxification, and adaptation, were investigated. A total of ten target proteins were shortlisted for further study, identified as follows: <i>BpoC</i>, <i>RipA</i>, <i>MazF4</i>, <i>RipD</i>, <i>TB15.3</i>, <i>VapC15</i>, <i>VapC20</i>, <i>VapC21</i>, <i>TB31.7</i>, and <i>MazF9</i>. Molecular docking studies showed that <i>β</i>-amyrin interacted with most of these proteins and its highest binding affinity was observed with <i>Mycobacterium</i> Rv1636 (<i>TB15.3</i>) protein. The stability of the protein-ligand complex was assessed by molecular dynamic simulation, which confirmed that <i>β</i>-amyrin most firmly interacted with <i>Rv1636</i> protein. <i>Rv1636</i> is a universal stress protein, which regulates <i>Mycobacterium</i> growth in different stress conditions and, thus, targeting <i>Rv1636</i> makes <i>M. tuberculosis</i> vulnerable to host-derived stress conditions.