title: Novel Insight from Computational Virtual Screening Depict the Binding Potential of Selected Phytotherapeutics Against Probable Drug Targets of Clostridium difficile.
abstract: This study explores computational screening and molecular docking approaches to screen novel herbal therapeutics against probable drug targets of Clostridium difficile. The essential genes were predicted by comparative genome analysis of C. difficile and best homologous organisms using BLAST search at database of essential genes (DEG). The functions of these genes in various metabolic pathways were predicted and some of these genes were considered as potential targets. Three major proteins were selected as putative targets, namely permease IIC component, ABC transporter and histidine kinase. The three-dimensional structures of these targets were predicted by molecular modelling. The herbal bioactive compounds were screened by computer-aided virtual screening and binding potentials against the drug targets were predicted by molecular docking. Quercetin present in Psidium guajava (binding energy of -9.1 kcal/mol), Ellagic acid found in Punica granatum and Psidium guajava (binding energy -9.0 kcal/mol) and Curcumin, present in Curcuma longa (binding energy -7.8 kcal/mol) demonstrated minimum binding energy and more number of interacting residues with the drug targets. Further, comparative study revealed that phytoligands demonstrated better binding affinities to the drug targets in comparison with usual ligands. Thus, this investigation explores the therapeutic probabilities of selected phytoligands against the putative drug targets of C. difficile.
authors.affiliation: Department of Biotechnology Engineering, R & D Centre, Dayananda Sagar Institutions, Bangalore, 560 078, India.|Visvesvaraya Technological University, Belagavi, Karnataka, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Kamath
authors.affiliation: Department of Biotechnology Engineering, R & D Centre, Dayananda Sagar Institutions, Bangalore, 560 078, India. sinoshskariya@gmail.com.|Visvesvaraya Technological University, Belagavi, Karnataka, India. sinoshskariya@gmail.com.
authors.forename: Sinosh
authors.initials: S
authors.lastname: Skariyachan
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry; D016360:Clostridioides difficile / Q000187:drug effects* / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D005798:Genes, Bacterial; D020043:Genes, Essential; D008024:Ligands; D053858:Metabolic Networks and Pathways; D062105:Molecular Docking Simulation; D010802:Phylogeny; D064209:Phytochemicals / Q000494:pharmacology*; D008517:Phytotherapy; D018675:Toxicity Tests; D014584:User-Computer Interface
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008024:Ligands; D064209:Phytochemicals
keywords: Clostridium difficile; Essential genes; Metabolic pathways; Molecular docking; Molecular modelling; Phytoligands; Putative drug targets