Repurposing of FDA approved drugs and their validation against potential drug targets for Salmonella enterica through molecular dynamics simulation

Abstract

Salmonella is a widely distributed pathogen causing infection of intestinal tract, typhoid, and paratyphoid fever. Number of drugs was developed against salmonella, but in the last few decades due to the emergence of drug resistant strains, most of these drugs became dormant. As a result Salmonellosis emerges as a trivial cause of human mortality worldwide; therefore, there is an urgent need for unexploited drug targets and drugs to treat Salmonellosis. As development of new drug molecules is very time consuming and costly, drug repurposing is in consideration as a better alternative. With the aim to identify a new drug molecule against the Salmonella through repurposing approach, we utilized 14 well reported druggable targets known to play a vital role in the life cycle of pathogens. These targets were used to screen DrugBank and got 53 FDA approved drugs against them. To find the interaction between considered target proteins and screened drugs, molecular docking was performed. Fourteen docked drug-target complexes with reasonable binding affinities were subjected to Molecular Dynamics Simulation (MDS) at 150 ns, using Amber18. At the end MMPBSA and MMGBSA calculations were performed for all stable complexes and finally, got 3 precise and favourable complexes, i.e. ArcB-Cefpiramide, MrcB-Cefoperazone, and PhoQ-Carindacillin. Rigorous structural and energetic analysis for these complexes validates the potential of drug molecules to act as therapeutic drugs against Salmonella enterica. With this study we hypothesize that the drugs Cefpiramide (DB00430), Cefoperazone (DB01329) and Carindacillin (DB09319) will be the good repurposed-drugs for the treatment of Salmonellosis.

Communicated by Ramaswamy H. Sarma

Keywords:

• Docking
• drug repurposing
• molecular dynamics simulation
• Salmonellosis
• Salmonella

Acknowledgements

Authors are thankful to Supercomputing Facility for Bioinformatics and Computational Biology (SCFBio).

Disclosure statement

All the authors collectively declare that there is no conflict of interest.