title: Identification of Potential Therapeutics to Conquer Drug Resistance in Salmonella typhimurium: Drug Repurposing Strategy.
abstract: BACKGROUND
  Salmonella typhimurium is the main cause of gastrointestinal illness in humans, and treatment options are decreasing because drug-resistant strains have emerged.
  
  
  OBJECTIVE
  The objective of this study was to use computational drug repurposing to identify a novel candidate with an effective mechanism of action to circumvent the drug resistance.
  
  
  METHODS
  We used the Mantra 2.0 database to initially screen drug candidates that share similar gene expression profiles to those of quinolones. Data were further reduced using pharmacophore mapping theory. Finally, we employed molecular-simulation studies to calculate the binding affinity of the screened candidates with DNA gyrase, alongside an analysis of side effects.
  
  
  RESULTS
  A total of 16 drug candidates from the Mantra 2.0 database were screened. The pharmacophoric features of the screened candidates were examined and nalidixic acid features compared using the PharamGist program. A total of 11 compounds with the highest pharmacophore score were considered for binding energy calculation. Finally, we analysed the side effects of the eight drug candidates that showed significant binding affinity in the simulation study.
  
  
  CONCLUSIONS
  Overall, flufenamic acid and sulconazole may be potential drug candidates that could be studied in vitro to assess their resistance profile against Salmonella enterica Typhimurium.
authors.affiliation: Department of Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India.
authors.forename: Balasundaram
authors.initials: B
authors.lastname: Preethi
authors.affiliation: Department of Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India.
authors.forename: Veerappapillai
authors.initials: V
authors.lastname: Shanthi
authors.affiliation: Department of Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India. kramanathan@vit.ac.in.
authors.forename: Karuppasamy
authors.initials: K
authors.lastname: Ramanathan
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D027081:DNA Gyrase / Q000737:chemistry / Q000378:metabolism; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D058492:Drug Repositioning / Q000379:methods*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005439:Flufenamic Acid / Q000378:metabolism / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D062105:Molecular Docking Simulation; D015203:Reproducibility of Results; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000472:pathogenicity; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D007093:Imidazoles; D059005:Topoisomerase II Inhibitors; C033308:sulconazole; D005439:Flufenamic Acid; D027081:DNA Gyrase