Molecular Docking Simulation-based Pharmacophore Modeling to Design Translation Inhibitors Targeting c-di-GMP Riboswitch of Vibrio cholera

Abstract

Background: Vibrio cholera is a facultative pathogenic bacterium that causes cholera pandemics, primarily in nations with hot and humid climates and large bodies of water containing a large quantity of organic debris. Consumption of V. cholera contaminated water or food causes acute diarrheal illness, followed by severe dehydration and mortality. Cholera is a highly infectious illness, with over 4 million cases recorded globally each year, and over a hundred thousand deaths. Objective: The only known therapy for cholera infection is oral rehydration solution along with antibiotics. Excessive antibiotic use causes pathogens to acquire antimicrobial drug resistance, resulting in a loss of efficacy. Furthermore, antibiotics are accompanied with a plethora of unfavorable side effects, restricting their usage. Methods: A Riboswitch is a non-homologous proteinaceous therapeutic target that plays a regulatory role in the crucial process of bacterial translation. As a result, the bacterial riboswitch was investigated as a surrogate target for developing a therapeutic medication against V. cholera. Results: In-silico screening with 24407 ligands was performed against the bacterial riboswitch to identify potential lead candidates, followed by pharmacophore modeling and bioisosteric lead modifications to design potential leads having an antagonistic impact on the pathogenic bacterial riboswitch Conclusion: The riboswitch-based innovative therapy was anticipated to be devoid of the issues connected with the development of antimicrobial drug resistance as well as the unwanted side effects associated with antibiotic usage.