**5. Conclusions**

The effect of the phytoconstituents of *C. procera*, *C. gigantea* and *A. aspera* plant extracts on the *M. tuberculosis* H37Rv cell proteins was investigated in this study. The phytochemical analysis of all plant extracts showed the presence of a significant content of phenols and flavonoids, especially in the ethyl acetate fraction of *A. aspera* and the ash of *C. gigantea* fractions. The plants extracts were tested against different mycobacterial strains. *A. aspera* aerial and *C. gigantea* flower ash was found to be active against the *M. tuberculosis* H37Rv ATCC 27294 strains with an MIC value of 64 mg/L. A multitarget assessment study was used to identify the possible mycobacterial target proteins. Ten proteins, viz. *BpoC*, *RipA*, *MazF4*, *RipD*, *TB15.3*, *VapC15*, *VapC20*, *VapC21*, *TB31.7*, *MazF9*, were found in the intersection of two categories, viz. available PDB dataset proteins and proteins classified in virulence, detoxification, adaptation. In silico characterization identified *TB15.3* (Rv1636) in the intersection of PPI network, which are the universal stress proteins. The phylogenetic analysis showed Rv1636 is a conserved protein among different mycobacterial strains. The molecular docking study of *β*-amyrin revealed its highest binding affinity with *Rv1636*. Furthermore, MD simulation was used to determine the stability and accuracy of the complex and it showed that the complex of *β*-amyrin and *Rv1636* was a stable complex, and the protein did not undergo unfolding during the simulation run. On a final note, this study established a significant bridge in the field of mycobacterial biology, which focused on targeting Rv1636, a universal stress protein of mycobacteria, through natural phytoconstituents.

**Supplementary Materials:** The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules27144581/s1, Table S1: Minimum inhibitory concentration (MIC) of different plants extracts in various solvent fractions against *M. tuberculosis* strains; Figure S1: Venn-diagram to categorize V.D.A category and known *Mtb* PDB structure protein; Figure S2: Crystal structure of selected *M. tuberculosis* H37Rv proteins (PDB: 7LD8, 4Q4N, 5XE2, 4LJ1, 1TQ8, 4CHG, 5WZ4, 2JAX, 5SV2, 6L2A); Figure S3: In multitarget protein docking, the top hit selected phytoconstituents; Table S2: List of the bioinformatics tools and databases for learning substantial outcome of Hypothetical protein from *M. tuberculosis* H37Rv; Table S3: Phytochemical constituents identified in the ethyl acetate aerial part extract of *A. aspera* using gas chromatography–mass spectrometry; Table S4: Phytochemical constituents identified in the ethyl acetate flower ash extract of *C. gigantea* using gas chromatography–mass spectrometry; Table S5: Physiochemical parameters of selected virulence, detoxification, adaptation category proteins; Table S6: Secondary structure analysis of selected virulent proteins of *Mtb*; Table S7: Selected hits and their binding free energies (kcal/mol) toward multiple target proteins; and Table S8: Selected compounds and their biological properties.

**Author Contributions:** M.A.B.: Conceptualization, Methodology, Software, Formal analysis, Data curation, Writing—original draft; S.: Methodology, Data curation, Writing—review & editing; O.A.: Methodology, Formal analysis, Data curation, Writing—review & editing. M.S.A.: Methodology, Software, Formal analysis, Project administration; A.S.A.A.: Software, Formal analysis, Data curation; A.H.: Formal analysis, Data curation, Writing—review & editing; M.A.I.: Methodology, Software, Formal analysis, Data curation; M.N.A.: Methodology, Formal analysis, Data curation, Writing—review & editing; S.C.: Methodology, Formal analysis, Data curation, Writing—review & editing; F.A.: Conceptualization, Supervision. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work is supported by the Deanship of Scientific Research, King Khalid University, Saudi Arabia [Grant number RGP.1/242/43].

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The data that supports the findings of this study are contained within the article and supporting information.

**Acknowledgments:** The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through Small Groups. (Project under grant number RGP.1/242/43).

**Conflicts of Interest:** The authors declare no conflict of interest.

**Sample Availability:** Not applicable.
