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

• Published in: Heliyon Vol. 9; no. 6; p. e17026
• Main Authors: Bappy, Md Nazmul Islam, Robin, Tanjin Barketullah, Prome, Anindita Ash, Patil, Rajesh B, Moin, Abu Tayab, Akter, Rupali, Laskar, Fayeza Sadia, Roy, Anindita, Akter, Hafsa, Zinnah, Kazi Md Ali
• Format: Journal Article
• Language: English
• Published: England Elsevier 01.06.2023
• Subjects: Candida auris; Drug targets; In silico approach; MD simulation; Molecular docking; Potential drugs; MD simulation; Candida auris; Potential drugs; Drug targets; In silico approach; Molecular docking
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2023.e17026

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 study of this pathogen to discover possible targets for drug design and also recommended some possible metabolites to test 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  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 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.