Identification of Therapeutic Targets in an Emerging Gastrointestinal Pathogen Campylobacter ureolyticus and Possible Intervention through Natural Products
Kanwal Waseem Khan,Zarrin Basharat,Khurshid Jalal,Mutaib M Mashraqi,Ahmad A. Alzamami,Saleh Alshamrani,Reaz Uddin +6 more
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TLDR
The findings of this report may serve as baseline information for laboratory studies leading to the discovery of drugs for use against C. ureolyticus infections and help identify potential risks associated with the selected compounds.Abstract:
Campylobacter ureolyticus is a Gram-negative, anaerobic, non-spore-forming bacteria that causes gastrointestinal infections. Being the most prevalent cause of bacterial enteritis globally, infection by this bacterium is linked with significant morbidity and mortality in children and immunocompromised patients. No information on pan-therapeutic drug targets for this species is available yet. In the current study, a pan-genome analysis was performed on 13 strains of C. ureolyticus to prioritize potent drug targets from the identified core genome. In total, 26 druggable proteins were identified using subtractive genomics. To the best of the authors’ knowledge, this is the first report on the mining of drug targets in C. ureolyticus. UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) was selected as a promiscuous pharmacological target for virtual screening of two bacterial-derived natural product libraries, i.e., postbiotics (n = 78) and streptomycin (n = 737) compounds. LpxC inhibitors from the ZINC database (n = 142 compounds) were also studied with reference to LpxC of C. ureolyticus. The top three docked compounds from each library (including ZINC26844580, ZINC13474902, ZINC13474878, Notoginsenoside St-4, Asiaticoside F, Paraherquamide E, Phytoene, Lycopene, and Sparsomycin) were selected based on their binding energies and validated using molecular dynamics simulations. To help identify potential risks associated with the selected compounds, ADMET profiling was also performed and most of the compounds were considered safe. Our findings may serve as baseline information for laboratory studies leading to the discovery of drugs for use against C. ureolyticus infections.read more
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Integrated Bioinformatics-Based Subtractive Genomics Approach to Decipher the Therapeutic Drug Target and Its Possible Intervention against Brucellosis
Kanwal Waseem Khan,Munirah Sulaiman Othman Alhar,Muhammad Naseer Abbas,Syed Qamar Abbas,M. S. Kazi,Saeed A. Khan,Abdulateef Omoniyi Sadiq,Syed Shams ul Hassan,Simona Bungau,Khurshid Jalal +9 more
TL;DR: In this article , the authors explore the complete Brucella suis proteome to prioritize the novel proteins as drug targets via subtractive proteo-genomics analysis, an effort to conjecture the existence of distinct pathways in the development of brucellosis.
Journal ArticleDOI
Pan-Genomics of Escherichia albertii for Antibiotic Resistance Profiling in Different Genome Fractions and Natural Product Mediated Intervention: In Silico Approach
Khurshid Jalal,Kanwal Waseem Khan,Ajmal Hayat,Sulaiman Alnasser,Alotaibi Meshal,Zarrin Basharat +5 more
TL;DR: In this paper , a comprehensive in silico strategy was followed to first list out antibiotic-resistant genes from core, accessory and unique genome fractions of 95 available genomes of E. albertii.
Journal ArticleDOI
Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics
TL;DR: Wang et al. as discussed by the authors used pan-genome and subtractive proteomics to identify new antimicrobial targets for Vibrio parahaemolyticus and to identify the effect of Actinomycin D.
Journal ArticleDOI
Inferring Therapeutic Targets in Candida albicans and Possible Inhibition through Natural Products: A Binding and Physiological Based Pharmacokinetics Snapshot
Zarrin Basharat,Kanwal Waseem Khan,Khurshid Jalal,Sulaiman Alnasser,Sania Majeed,Marium Zehra +5 more
TL;DR: In this paper , the authors attempted to mine drug targets (n = 46) using a subtractive proteomic approach in this pathogenic yeast and screen natural products with inhibition potential against fructose-bisphosphate aldolase (FBA) of C. albicans.
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