Identification of Potent Natural Resource Small Molecule Inhibitor to Control <i>Vibrio cholera</i> by Targeting Its Outer Membrane Protein U: An In Silico Approach
Abdul Rahaman,
Abdulraheem Ali Almalki,
Misbahuddin M. Rafeeq,
Omar Akhtar,
Farah Anjum,
Mutaib M. Mashraqi,
Ziaullah M. Sain,
Ahmad Alzamami,
Varish Ahmad,
Xin-An Zeng,
Qazi Mohammad Sajid Jamal
Affiliations
Abdul Rahaman
College of Food Science and Engineering, Foshan University, Foshan 528231, China
Abdulraheem Ali Almalki
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box Number 11099, Taif 21944, Saudi Arabia
Misbahuddin M. Rafeeq
Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Omar Akhtar
Department of Medicine, Tbilisi State Medical University, Tbilisi 0177, Georgia
Farah Anjum
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box Number 11099, Taif 21944, Saudi Arabia
Mutaib M. Mashraqi
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia
Ziaullah M. Sain
Department of Microbiology, Faculty of Medicine, Rabigh, King Abduaziz University, Jeddah 21589, Saudi Arabia
Ahmad Alzamami
Clinical Laboratory Science Department, College of Applied Medical Science, Shaqra University, Shaqra 11961, Saudi Arabia
Varish Ahmad
Health Information Technology Department, Faculty of Applied Studies, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Xin-An Zeng
College of Food Science and Engineering, Foshan University, Foshan 528231, China
Qazi Mohammad Sajid Jamal
Department of Health Informatics, College of Public Health and Health Informatics, Qassim University, Al Bukayriyah 52741, Saudi Arabia
Vibrio cholerae causes the diarrheal disease cholera which affects millions of people globally. The outer membrane protein U (OmpU) is the outer membrane protein that is most prevalent in V. cholerae and has already been recognized as a critical component of pathogenicity involved in host cell contact and as being necessary for the survival of pathogenic V. cholerae in the host body. Computational approaches were used in this study to screen a total of 37,709 natural compounds from the traditional Chinese medicine (TCM) database against the active site of OmpU. Following a sequential screening of the TCM database, we report three lead compounds—ZINC06494587, ZINC85510056, and ZINC95910434—that bind strongly to OmpU, with binding affinity values of −8.92, −8.12, and −8.78 kcal/mol, which were higher than the control ligand (−7.0 kcal/mol). To optimize the interaction, several 100 ns molecular dynamics simulations were performed, and the resulting complexes were shown to be stable in their vicinity. Additionally, these compounds were predicted to have good drug-like properties based on physicochemical properties and ADMET assessments. This study suggests that further research be conducted on these compounds to determine their potential use as cholera disease treatment.
