In silico study of phytochemicals as potential inhibitors against the toxic protein (hemolysin e) in salmonella typhi a causative agent of typhoid
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Date
2019
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UMT, Lhr
Abstract
Typhoid fever, which is caused by Salmonella enterica serovar Typhi, remains a major public health threat in developing countries. It is an important cause of morbidity and mortality globally. It is transmitted through the ingestion of contaminated food and water exposed by the faeces or urine of infected people. Salmonella typhi, has developed multidrug resistance (MDR) to a wide range of antibacterial classes. This has led to higher degrees of concern among researchers, as Salmonella typhi has begun to show increasing resistance to current antibiotics, leading the bacterium to be on the verge of being classified within the superbug family. Recently phytochemicals are being considered as potential inhibitors against typhoid fever in human beings. The study was carried out to identify as many as possible potent and selective inhibitors with great potential of binding and inhibition against Hemolysin- E (leading cause of Typhoid fever). Medicinal plants are used for this purpose to obtain phytochemicals as inhibitors from them. ADMET (Absorption, Distribution, metabolism, Excretion and Toxicity) analysis, Homology Modelling and Molecular docking were used as a computational method to evaluate the drug likeliness binding energies, and ligand-receptor complex with optimized conformation to observe the reaction of small molecule in the binding pocket of target protein. A threshold was set for hemolysin E protein i.e. -5.99 kcal/mol so that we can compare the efficacy of novel phytochemicals with previously reported phytochemicals. Most Stable binding affinity showed by phytochemical against Hemolysin E protein with minimum binding energy -9.2kcal/mol. The phytochemicals which showed this stable affinity was JacarelhyperolB. The Ki value for this compound was 0.177µM. Next to this, three compounds having stable binding affinities were Quercetin3-O-(beta-Dxylopyranosyl(1-2)-alpha-L-rhamnopyranosyl(1-6))-beta-D-galactopyranoside, JacarelhyperolA, and typhaneoside with their binding energies -8.2, -8.4 and -8.0 kcal / mol. The Ki value forthis compound was 0.961, 0.685 and 1.347µM. In silico analysis of phytochemicals exposed four compounds after making comparison with previously reported phytochemicals as novel inhibitors against Hemolysin- E of Salmonela typhi. So all these four phytochemicals can be safely considered for further in vivo and in vitro analysis for the clinical development of drugs against Typhoid fever.