Unveiling novel antibacterials through DNA sequence analysis and molecular docking leads to gyrB gene ATP binding pocket inhibition of E.coli that is isolated from UTI

Background: Escherichia coli, which normally lives in the colon, is the most common cause of urinary tract infections (UTI), accounting for 80-85% of community-acquired infections. This research aims to study the three-dimensional shapes of the gyrB gene, identify the region of the ATP binding pocket, and discover new antibacterials that can bind to this pocket and inhibit the action of DNA gyrase enzyme in E.coli bacteria, due to the development of the bacteria and its resistance to antibiotics. Methods: In hospitals of the Holy Kerbala Governorate (Imam Al-Hussein teaching , Imam Al-Hassan Al-Mujtaba, Obstetrics and Gynecology Hospital, and Imam Al-Hujjah Charitable Hospital) 223 specimens were collected from patients with symptoms of UTI, according to standard procedure, and urine culture was performed. The bacteria were then identified using API 20E test. The gyrB gene was then amplified, sequenced and examined using bioinformatics techniques. The region of the enzyme's ATP binding pocket was identified and its three-dimensional shape was examined. Afterward, chemical compounds were proposed by using molecular docking to attach to this pocket. Results: 60 out of the 223 specimens had urinary tract infection symptoms had an E.coli infection. The sequence alignment of nitrogenous bases in the gyrB gene was 99–100% comparable to the global sequences of the same bacterium, according to molecular analysis. It demonstrated 99–100% similarity to the global sequences for amino acids as well. Additionally, several suggested chemical compounds, such as Dieckol, Robinin, Quercitrin, Vitamin D3, Vitamin D2, Myricitrin, and Daidzin have high docking scores with the ATP binding pocket (Which was determined by previous research working in this field) and some have weak docking scores with the ATP binding pocket such as Scopoline, Crocin, Allicin and Propionic acid. Then the compounds with high docking scores were submitted to Lipinski's rule of five to know the chemical compounds most suitable for oral administration, where it was found that the compounds Daidzin, Dalbergin, Quercitrin, Cyproheptadine, Piroxicam, and others are the most suitable compounds for oral administration and for inhibiting the ATP binding pocket of the gyrB gene of E.coli. Conclusions: Diadzin, Ketotifen, Cyproheptadin, Dalbergin, Piroxicam, Etodolac, Frangulin A, Chrysin, Quercitrin, Myricetin, Peonidin, Flavan-4-ol, Lutin, Emodine, Aurone, Baicalein, and Phaseollidine They are promising compounds that may inhibit the ATP binding domain in the gyrB gene of E.coli