Identification of Potential Therapeutics to Conquer Drug Resistance in Salmonella typhimurium: Drug Repurposing Strategy
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Salmonella typhimurium is the main cause of gastrointestinal illness in humans, and treatment options are decreasing because drug-resistant strains have emerged.
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.
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.
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.
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.
KeywordsProtein Data Bank Nalidixic Acid Molecular Docking Study Tiapride Flufenamic Acid
The authors thank the management of VIT University for providing the facility, support, and constant encouragement to carry out this work.
Compliance with Ethical Standards
No sources of funding were used to assist in the preparation of this study.
Conflicts of interest
B. Preethi, V. Shanthi and K. Ramanathan have no conflicts of interest.
- 16.Gibson CC, Zhu W, Davis CT, Bowman-Kirigin JA, Chan AC, Ling J, Walker AE, Goitre L, Delle Monache S, Retta SF, Shiu YT, Grossmann AH, Thomas KR, Donato AJ, Lesniewski LA, Whitehead KJ, Li DY. Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Circulation. 2015;131:289–99.CrossRefPubMedGoogle Scholar
- 17.Veljkovic V, Loiseau PM, Figadere B, Glisic S, Veljkovic N, Perovic VR, Cavanaugh DP, Branch DR. Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection. F1000Res. 2015;4:34.Google Scholar
- 22.Webb B, Sali A. Comparative protein structure modeling using MODELLER. Curr Protoc Bioinform. 2016;54:5.6.1–5.6.37.Google Scholar
- 39.Bassily S, Hyams KC, el-Masry NA, Farid Z, Cross E, Bourgeois AL, Ayad E, Hibbs RG. Short-course norfloxacin and trimethoprim-sulfamethoxazole treatment of shigellosis and salmonellosis in Egypt. Am J Trop Med Hyg. 1994;51:219–223.Google Scholar
- 41.Eaves DJ, Randall L, Gray DT, Buckley A, Woodward MJ, White AP, Piddock LJ. Prevalence of mutations within the quinolone resistance-determining region of gyrA, gyrB, parC, and parE and association with antibiotic resistance in quinolone-resistant Salmonella enterica. Antimicrob Agents Chemother. 2004;48:4012–5.CrossRefPubMedPubMedCentralGoogle Scholar