Insight into novel inhibitors from Sterculia urens against Cholera via pharmacoinformatics and molecular dynamics simulation approaches

Abstract

The underdeveloped countries with large populations are facing a grave global threat in the form of cholera. Vibrio cholerae, the etiologic agent of Cholera has drawn attention recently due to antimicrobial resistance and resulting outbreaks that necessitates establishment of novel medications to counteract virulence and viability of the pathogen. Sterculia urens Roxb. (Malvaceae) is an ethnomedicinally important tree, which harbors a good number of bioactive phytocompounds. In the present study, 53 phytocompounds of S. urens were screened against the promising target ToxT of V. cholerae employing structure-based drug design approach that revealed three lead compounds, viz., 4,4,5,8-Tetramethylchroman-2-ol (−8.2 kcal/mol), Beta-Bisabolol (−8.2 kcal/mol) and Ledol (−8.7 kcal/mol) with satisfactory ADMET properties. Molecular dynamics simulation for 150 ns unveiled notable compactness and structural stability for the lead compounds considering RMSD, RMSF, Rg, MolSA, PSA and protein-ligand contacts parameters. Molecular mechanics-based MM/GBSA binding energy calculation revealed Beta-Bisabolol (−66.74 kcal/mol) to have better scores than 4,4,5,8-Tetramethylchroman-2-ol (−47.42 kcal/mol) and Ledol (−65.79 kcal/mol). Enzymes were mostly found as drug target class, and Nabilone was found as a structurally similar analog for 4,4,5,8-Tetramethylchroman-2-ol. These discoveries could aid in revealing new antibacterial medications targeting ToxT to combat Cholera.

Communicated by Ramaswamy H. Sarma

Keywords:

• Sterculia urens
• cholera
• ToxT protein
• molecular docking
• mM/GBSA

Acknowledgement

The authors are thankful to the Researchers Supporting Project number (RSP2023R132), King Saud University, Riyadh, Saudi Arabia for supporting the study.

Author contributions

Conceptualization and design: M.O.R. and S.S.A.; Writing – Original Draft Preparation: S.S.A.; Writing – Review & Editing: M.O.R., U.C. and A.S.A.; Methodology: S.S.A. and M.O.R.; Software: S.S.A. and M.A.A.; Validation: M.O.R. and A.S.A.; Formal Analysis: S.S.A.; Data Curation: S.S.A. and M.O.R.; Visualization: S.S.A., M.O.R., M.A.A. and U.C.; Supervision and Project Administration: M.O.R.; Funding Acquisition: A.S.A.; and final approval of the manuscript: all authors.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was funded by King Saud University Researchers Supporting Project (RSP2023R132), King Saud University, Saudi Arabia.