Subtractive proteomics analysis to uncover the potent drug targets for distinctive drug design of Candida auris .

Autor:	Bappy MNI; Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet-3100, Bangladesh.; Department of Animal and Fish Biotechnology, Sylhet Agricultural University, Sylhet-3100, Bangladesh., Robin TB; Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet-3100, Bangladesh., Prome AA; Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet-3100, Bangladesh., Patil RB; Department of Pharmaceutical Chemistry, Sinhgad Technical Education Society's, Sinhgad College of Pharmacy, Off Sinhgad Road, Vadgaon (Bk), Pune 411041, Maharashtra, India., Moin AT; Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram, Bangladesh., Akter R; Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Chittagong, Chattogram, Bangladesh., Laskar FS; Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet-3100, Bangladesh., Roy A; Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet-3100, Bangladesh., Akter H; Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet-3100, Bangladesh.; Department of Biochemistry and Chemistry, Sylhet Agricultural University, Sylhet-3100, Bangladesh., Zinnah KMA; Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet-3100, Bangladesh.; Department of Animal and Fish Biotechnology, Sylhet Agricultural University, Sylhet-3100, Bangladesh.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2023 Jun 06; Vol. 9 (6), pp. e17026. Date of Electronic Publication: 2023 Jun 06 (Print Publication: 2023).
DOI:	10.1016/j.heliyon.2023.e17026
Abstrakt:	Candida auris is a serious health concern of the current world that possesses a serious global health threat and is emerging at a high rate. Available antifungal drugs are failing to combat this pathogen as they are growing resistant to those drugs and some strains have already shown resistance to all three available antifungal drugs in the market. Hence, finding alternative therapies is essential for saving lives from this enemy. To make the development of new treatments easier, we conducted some in silico study of this pathogen to discover possible targets for drug design and also recommended some possible metabolites to test in vivo circumstances. The complete proteome of the representative strain was retrieved, and the duplicate, non-essential, human homologous, non-metabolic, and druggable proteins were then eliminated. As a result, out of a total of 5441  C. auris proteins, we were able to isolate three proteins (XP 028890156.1, XP 028891672.1, and XP 028891858.1) that are crucial for the pathogen's survival as well as host-non-homolog, metabolic, and unrelated proteins to the human microbiome. Their subcellular locations and interactions with a large number of proteins (10 proteins) further point to them being good candidates for therapeutic targets. Following in silico docking of 29 putative antifungals of plant origin against the three proteins we chose, Caledonixanthone E, Viniferin, Glaucine, and Jatrorrhizine were discovered to be the most effective means of inhibiting those proteins since they displayed higher binding affinities (ranging from -28.97 kcal/mol to -51.99 kcal/mol) than the control fluconazole (which ranged between -28.84 kcal/mol and -41.15 kcal/mol). According to the results of MD simulations and MM-PBSA calculations, Viniferin and Caledonixanthone E are the most effective ligands for the proteins XP 028890156.1, XP 028891672.1, and XP 028891858.1. Furthermore, they were predicted to be safe and also showed proper ADME properties. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Authors.)
Databáze:	MEDLINE
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