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Anti-tubercular activity evaluation of natural compounds by targeting Mycobacterium tuberculosis resuscitation promoting factor B inhibition: An in silico study

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Abstract

Tuberculosis (TB), an infectious disease caused by the Mycobacterium tuberculosis (Mtb), has been responsible for the deaths of millions of individuals around the globe. A vital protein in viral pathogenesis known as resuscitation promoting factor (RpfB) has been identified as a potential therapeutic target of anti-tuberculosis drugs. This study offered an in silico process to examine possible RpfB inhibitors employing a computational drug design pipeline. In this study, a total of 1228 phytomolecules were virtually tested against the RpfB of Mtb. These phytomolecules were sourced from the NP-lib database of the MTi-OpenScreen server, and five top hits (ZINC000044404209, ZINC000059779788, ZINC000001562130, ZINC000014766825, and ZINC000043552589) were prioritized for compute intensive docking with dock score ≤ − 8.5 kcal/mole. Later, molecular dynamics (MD) simulation and principal component analysis (PCA) were used to validate these top five hits. In the list of these top five hits, the ligands ZINC000044404209, ZINC000059779788, and ZINC000043552589 showed hydrogen bond formation with the functional residue Glu292 of the RpfB protein suggesting biological significance of the binding. The RMSD study showed stable protein–ligand complexes and higher conformational consistency for the ligands ZINC000014766825, and ZINC000043552589 with RMSD 3–4 Å during 100 ns MD simulation. The overall analysis performed in the study suggested promising binding of these compounds with the RpfB protein of the Mtb at its functional site, further experimental investigation is needed to validate the computational finding.

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All data generated or analysed during this study are included in this published article.

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Funding

This study is supported via funding from Prince Sattam bin Abdulaziz University project number (PSAU/2023/R/1444).

Author information

Authors and Affiliations

  1. Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, 31311, Saudi Arabia

    Ali A. Rabaan

  2. College of Medicine, Alfaisal University, Riyadh, 11533, Saudi Arabia

    Ali A. Rabaan

  3. Department of Public Health and Nutrition, The University of Haripur, Haripur, 22610, Pakistan

    Ali A. Rabaan

  4. Department of Community Medicine and Health Care for Pilgrims, Faculty of Medicine, Umm Al-Qura University, Makkah, 21955, Saudi Arabia

    Mohammed Garout

  5. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Al Batin, Hafr Al Batin, 39831, Saudi Arabia

    Mohammed Aljeldah & Basim R. Al Shammari

  6. Department of Pediatrics, College of Medicine, Taibah University, Al-Madinah41491, Saudi Arabia

    Abdulsalam Alawfi & Amer Alshengeti

  7. Department of Infection prevention and control, Prince Mohammad Bin Abdulaziz Hospital, National Guard Health Affairs, Al-Madinah, 41491, Saudi Arabia

    Amer Alshengeti

  8. Department of Medical Laboratories Technology, College of Applied Medical Sciences, Taibah University, Madinah, 41411, Saudi Arabia

    Mustafa A. Najim

  9. Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra, 11961, Saudi Arabia

    Mohammed Alrouji & Yasir Almuhanna

  10. Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia

    Mohammed Alissa

  11. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, 61441, Saudi Arabia

    Mutaib M. Mashraqi

  12. Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, 51452, Saudi Arabia

    Ameen S. S. Alwashmi

  13. Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, 34212, Saudi Arabia

    Mashael Alhajri

  14. Microbiology laboratory, Central military Laboratory and Blood Bank, Prince Sultan Military Medical City, Riyadh, 11159, Saudi Arabia

    Souad Mohammed Alateah

  15. Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh, 33511, Egypt

    Ramadan Abdelmoez Farahat

  16. Department of Chemistry, Government College of Engineering, Keonjhar, 758002, India

    Ranjan K. Mohapatra

Authors
  1. Ali A. Rabaan
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  2. Mohammed Garout
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  3. Mohammed Aljeldah
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Contributions

Conceptualization, A.A.R. and R.K.M; Data curation, M.G., M.A. and B.R.A.S.; Formal analysis, A.A.R., M.G., M.A., B.R.A.S., A.A., M.A.N., M.A., Y.A., M.Ali, M.M.M., A.S.S.A., M.A., S.M.A., R.A.F.; Methodology, , A.A.R., M.G., M.A., B.R.A.S., A.A., M.A.N., M.A., Y.A., M.Ali, M.M.M., A.S.S.A., M.A., S.M.A., R.A.F.; Supervision, A.A.R. and R.K.M.; Validation, , A.A.R., M.G., M.A., B.R.A.S., A.A., M.A.N., M.A., Y.A., M.Ali, M.M.M., A.S.S.A., M.A., S.M.A., R.A.F.; Methodology, , A.A.R., M.G., M.A., B.R.A.S., A.A., M.A.N., M.A., Y.A., M. Ali, M.M.M., A.S.S.A., M.A., S.M.A., R.A.F., R.K.M.; Writing—original draft, A.A.R. and R.K.M.; All authors reviewed the manuscript.

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Correspondence to Ali A. Rabaan or Ranjan K. Mohapatra.

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Rabaan, A.A., Garout, M., Aljeldah, M. et al. Anti-tubercular activity evaluation of natural compounds by targeting Mycobacterium tuberculosis resuscitation promoting factor B inhibition: An in silico study. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10632-8

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