title: Exploring insights for virulent gene inhibition of multidrug resistant Salmonella typhi, Vibrio cholerae, and Staphylococcus areus by potential phytoligands via in silico screening.
abstract: In our recent studies on prevalence of multidrug resistant pathogens in Byramangala reservoir, Karnataka, India, we identified Salmonella typhi, Staphylococcus aureus, and Vibrio cholerae which had acquired multiple drug resistance (MDR) and emerged as superbugs. Hence, there is a pressing demand to identify alternative therapeutic remedies. Our study focused on the screening of herbal leads by structure-based virtual screening. The virulent gene products of these pathogens towards Kanamycin(aph), Trimethoprim(dfrA1), Methicillin (mecI), and Vancomycin (vanH) were identified as the probable drug targets and their 3D structures were predicted by homology modeling. The predicted models showed good stereochemical validity. By extensive literature survey, we selected 58 phytoligands and their drug likeliness and pharmacokinetic properties were computationally predicted. The inhibitory properties of these ligands against drug targets were studied by molecular docking. Our studies revealed that Baicalein from S. baicalensis (baikal skullcap) and Luteolin from Taraxacum officinale (dandelion) were identified as potential inhibitors against aph of S. typhi. Resveratrol from Vitis vinifera (grape vine) and Wogonin from S. baicalensis were identified as potential inhibitors against dfrA1 of S. typhi. Herniarin from Herniaria glabra (rupture worts) and Pyrocide from Daucus carota (Carrot) were identified as the best leads against dfrA1 of V. cholerae. Taraxacin of T. officinale (weber) and Luteolin were identified as potential inhibitors against Mec1. Apigenin from Coffee arabica (coffee) and Luteolin were identified as the best leads against vanH of S. aureus. Our findings pave crucial insights for exploring alternative therapeutics against MDR pathogens.
authors.affiliation: a R&D Centre, Department of Biotechnology , Dayananda Sagar College of Engineering , Bangalore 560 078 , Karnataka , India .
authors.forename: Sinosh
authors.initials: S
authors.lastname: Skariyachan
authors.forename: Nisha
authors.initials: N
authors.lastname: Jayaprakash
authors.forename: Navya
authors.initials: N
authors.lastname: Bharadwaj
authors.forename: Rajeswari
authors.initials: R
authors.lastname: Narayanappa
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D003198:Computer Simulation; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D008024:Ligands; D008958:Models, Molecular; D064209:Phytochemicals / Q000737:chemistry*; D012485:Salmonella typhi / Q000235:genetics* / Q000472:pathogenicity; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity; D014734:Vibrio cholerae / Q000235:genetics* / Q000472:pathogenicity; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D008024:Ligands; D064209:Phytochemicals; D037521:Virulence Factors
keywords: herbal leads; homology modeling; multidrug resistant pathogens; potential inhibitors; virtual screening; virulent genes