School of Medicine Publications and Presentations
Document Type
Article
Publication Date
6-16-2025
Abstract
Dormancy occurs when Mycobacterium tuberculosis (Mtb) enters a non-replicating and metabolically inactive state in response to hostile environment. During this state, it is highly resistant to conventional antibiotics, which increase the urgency to develop new potential drugs against dormant bacilli. In view of this, the dormancy survival regulator (DosR) protein is thought to be an essential component that plays a key role in bacterial adaptation to dormancy during hypoxic conditions. Herein, the NP-lib database containing natural product compounds was screened virtually against the binding site of the DosR protein using the MTiopen screen web server. A series of computational analyses were performed, including redocking, intermolecular interaction analysis, and MDS, followed by binding free energy analysis. Through screening, 1000 natural product compounds were obtained with docking energy ranging from −8.5 to −4.1 kcal/mol. The top four lead compounds were then selected for further investigation. On comparative analysis of intermolecular interaction, dynamics simulation and MM/GBSA calculation revealed that M3 docked with the DosR protein (docking score = −8.1 kcal/mol, RMSD = ~7 Å and ΔG Bind = −53.51 kcal/mol) exhibited stronger stability than reference compound Ursolic acid (docking score = −6.2 kcal/mol, RMSD = ~13.5 Å and ΔG Bind = −44.51 kcal/mol). Hence, M3 is recommended for further validation through in vitro and in vivo studies against latent tuberculosis infection.
Recommended Citation
Chouhan, M., Kumar, M., Dwivedi, V. D., Kashyap, V. K., Singh, H. N., & Kumar, S. (2025). Harnessing Natural Product Compounds to Target Dormancy Survival Regulator (DosR) in Latent Tuberculosis Infection (LTBI): An In Silico Strategy Against Dormancy. Advances in Respiratory Medicine, 93(3), 19. https://doi.org/10.3390/arm93030019
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Advances in Respiratory Medicine
DOI
10.3390/arm93030019
Academic Level
faculty
Mentor/PI Department
Immunology and Microbiology
Comments
© 2025 by the authors. Published by MDPI on behalf of the Polish Respiratory Society. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).