title: Study of intra-inter species protein-protein interactions for potential drug targets identification and subsequent drug design for Escherichia coli O104:H4 C277-11.
abstract: Protein-protein interaction (PPI) and host-pathogen interactions (HPI) proteomic analysis has been successfully practiced for potential drug target identification in pathogenic infections. In this research, we attempted to identify new drug target based on PPI and HPI computation approaches and subsequently design new drug against devastating enterohemorrhagic Escherichia coli O104:H4 C277-11 (Broad), which causes life-threatening food borne disease outbreak in Germany and other countries in Europe in 2011. Our systematic in silico analysis on PPI and HPI of E. coli O104:H4 was able to identify bacterial D-galactose-binding periplasmic and UDP-N-acetylglucosamine 1-carboxyvinyltransferase as attractive candidates for new drug targets. Furthermore, computational three-dimensional structure modeling and subsequent molecular docking finally proposed [3-(5-Amino-7-Hydroxy-[1,2,3]Triazolo[4,5-D]Pyrimidin-2-Yl)-N-(3,5-Dichlorobenzyl)-Benzamide)] and (6-amino-2-[(1-naphthylmethyl)amino]-3,7-dihydro-8H-imidazo[4,5-g]quinazolin-8-one) as promising candidate drugs for further evaluation and development for E. coli O104:H4 mediated diseases. Identification of new drug target would be of great utility for humanity as the demand for designing new drugs to fight infections is increasing due to the developing resistance and side effects of current treatments. This research provided the basis for computer aided drug design which might be useful for new drug target identification and subsequent drug design for other infectious organisms.
authors.affiliation: Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh. shakhin200-gen@sust.edu.|Division of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan. shakhin200-gen@sust.edu.
authors.forename: Shakhinur Islam
authors.initials: SI
authors.lastname: Mondal
authors.affiliation: Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.
authors.forename: Zabed
authors.initials: Z
authors.lastname: Mahmud
authors.affiliation: Department of Diagnosis, Prevention and Treatment of Dementia, Juntendo University Graduate School of Medicine, Bunkyō, Tokyo, Japan.
authors.forename: Montasir
authors.initials: M
authors.lastname: Elahi
authors.affiliation: Division of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.|Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.
authors.forename: Arzuba
authors.initials: A
authors.lastname: Akter
authors.affiliation: Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.
authors.forename: Nurnabi Azad
authors.initials: NA
authors.lastname: Jewel
authors.affiliation: Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.
authors.forename: Md
authors.initials: M
authors.lastname: Muzahidul Islam
authors.affiliation: Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.
authors.forename: Sabiha
authors.initials: S
authors.lastname: Ferdous
authors.affiliation: Division of Parasitology, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692, Japan.
authors.forename: Taisei
authors.initials: T
authors.lastname: Kikuchi
keywords: Drug resistance; Homology modeling; Host–pathogen interactions; Molecular docking; Protein structure