An in-silico approach to target multiple proteins involved in anti-microbial resistance using natural compounds produced by wild mushrooms.

Autor:	Singh G; Section of Microbiology, Central Ayurveda Research Institute, Jhansi, Uttar Pradesh, India, 284003.; Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India, 110016., Hossain MA; Department of Pharmacy, Jagannath University, 9, 10 Chittaranjan Ave, Dhaka, 1100, Bangladesh., Al-Fahad D; Department of Pharmaceutical Sciences, College of Pharmacy, University of Thi-Qar, Iraq., Gupta V; Departments of Microbiology, Ram Lal Anand College, University of Delhi, Benito Juarez Road, New Delhi, 110021, India., Tandon S; Section of Microbiology, Central Ayurveda Research Institute, Jhansi, Uttar Pradesh, India, 284003., Soni H; Section of Microbiology, Central Ayurveda Research Institute, Jhansi, Uttar Pradesh, India, 284003., Narasimhaji CV; Section of Microbiology, Central Ayurveda Research Institute, Jhansi, Uttar Pradesh, India, 284003., Jaremko M; Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia., Emwas AH; Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia., Anwar MJ; Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, 51542, Saudi Arabia., Azam F; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah, 51452, Saudi Arabia.
Jazyk:	angličtina
Zdroj:	Biochemistry and biophysics reports [Biochem Biophys Rep] 2024 Oct 21; Vol. 40, pp. 101854. Date of Electronic Publication: 2024 Oct 21 (Print Publication: 2024).
DOI:	10.1016/j.bbrep.2024.101854
Abstrakt:	Bacterial resistance to antibiotics and the number of patients infected by multi-drug-resistant bacteria have increased significantly over the past decade. This study follows a computational approach to identify potential antibacterial compounds from wild mushrooms. Twenty-six known compounds produced by wild mushrooms were docked to assess their affinity with drug targets of antibiotics such as penicillin-binding protein-1a (PBP1a), DNA gyrase, and isoleucyl-tRNA synthetase (ILERS). Docking scores were further validated by multiple receptor conformer (MRC)-based docking studies. Based on the MRC-based docking results, eight molecules were shortlisted for ADMET analysis. Molecular dynamics (MD) simulations were further performed to evaluate the conformational stability of the ligand-protein complexes. Binding energies were computed by the gmx_MMPBSA method. The data were obtained in terms of root-mean square deviation, and root-mean square fluctuation justified the stability of Austrocortilutein A, Austrocortirubin, and Confluentin in complex with several proteins under physiological conditions. Among these, Austrocortilutein A displayed better binding affinity with PBP1a and ILERS when compared with their respective reference ligands. This study is preliminary and aims to help drive the search for compounds that have the capacity to overcome the anti-microbial resistance of prevalent bacteria, using natural compounds produced by wild mushrooms. Further experimental validation is required to justify the clinical use of the studied compounds. 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. (© 2024 The Authors.)
Databáze:	MEDLINE
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