title: Computer based screening for novel inhibitors against Vibrio cholerae using NCI diversity set-II: an alternative approach by targeting transcriptional activator ToxT.
abstract: Cholera is a severe diarrheal disease caused by Vibrio cholerae and remains as a major health risk in developing countries. The emergence and spread of multi-drug resistant V. cholerae strains during the past two decades is now a major problem in the treatment of cholera and have created the urgent need for the development of novel therapeutic agents. Targeting transcriptional factor is now a novel approach to tackle the development of multi-drug resistant strain. In the recent year virtual high throughput screening has emerged as a widely accepted powerful technology in the identification of novel and diverse lead. This study provides new insight to the search for new potent and selective inhibitors that still remains necessary to avoid the risk of possible resistance and reduce toxicity and side effects of currently available cholera drugs. The publications of high resolution X-ray structure of V. cholerae ToxT has open the way to the structure based virtual screening to identify new small molecular inhibitors which still remain necessary to avoid the risk of possible resistance and reduce toxicity and side effects of currently available cholera drugs. In this study we have performed structure based virtual screening approach using NCI diversity set-II to look for novel inhibitor of ToxT and proposed eight candidate compounds with high scoring function. Thus from complex scoring and binding ability it is elucidated that these compounds could be the promising inhibitors or could be developed as novel lead compounds for drug design against cholera.
authors.affiliation: Genetic Engineering and Biotechnology Department, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh, shakhin200-gen@sust.edu.
authors.forename: Shakhinur Islam
authors.initials: SI
authors.lastname: Mondal
authors.forename: Bijendra
authors.initials: B
authors.lastname: Khadka
authors.forename: Arzuba
authors.initials: A
authors.lastname: Akter
authors.forename: Pradip Kumar
authors.initials: PK
authors.lastname: Roy
authors.forename: Razia
authors.initials: R
authors.lastname: Sultana
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002771:Cholera / Q000188:drug therapy / Q000382:microbiology*; D002772:Cholera Toxin; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D018432:Drug Resistance, Multiple; D006801:Humans; D062105:Molecular Docking Simulation; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015533:Transcriptional Activation / Q000187:drug effects; D014734:Vibrio cholerae / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D014157:Transcription Factors; D002772:Cholera Toxin