1. Identification of Potent Natural Resource Small Molecule Inhibitor to Control Vibrio cholera by Targeting Its Outer Membrane Protein U: An In Silico Approach
- Author
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Qazi Mohammad Sajid Jamal, Abdulraheem S. A. Almalki, Xin-An Zeng, Omar Akhtar, Farah Anjum, Ziaullah M. Sain, Misbahuddin M Rafeeq, Ahmad Alzamami, Mutaib M Mashraqi, Abdul Rahaman, and Varish Ahmad
- Subjects
In silico ,Phytochemicals ,Molecular Conformation ,Pharmaceutical Science ,cholera ,Molecular Dynamics Simulation ,medicine.disease_cause ,Article ,Analytical Chemistry ,Structure-Activity Relationship ,QD241-441 ,vHTS ,Drug Discovery ,medicine ,natural compounds ,Humans ,Physical and Theoretical Chemistry ,OmpU ,Vibrio cholerae ,Biological Products ,Binding Sites ,biology ,Chemistry ,Organic Chemistry ,Active site ,Hydrogen Bonding ,Ligand (biochemistry) ,medicine.disease ,Small molecule ,Cholera ,molecular dynamics ,Anti-Bacterial Agents ,Molecular Docking Simulation ,Biochemistry ,Chemistry (miscellaneous) ,biology.protein ,Molecular Medicine ,Vibrio cholera ,Bacterial outer membrane ,Bacterial Outer Membrane Proteins ,Protein Binding - Abstract
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.
- Published
- 2021