In Silico Predictions of Pharmacokinetic, Toxicity, and Molecular Interactions of Fungal β-1, 3/1, 6-Glucans Oligosaccharides with Immune Cells Receptors
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Abstract
β-1, 3/1, 6-glucans are polysaccharides in fungi’s cell walls (yeast, mold, and mushrooms) known to promote an immune response. Recently, gamma irradiation has been used to cut β-glucan polysaccharides into oligosaccharides with improved solubility. However, their pharmacokinetic and toxicity profiles, and molecular interactions with immune cell receptors were unknown. This study aims to use in silico models to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and the interaction of fungal β-1, 3/1, 6-glucans oligosaccharides with neutrophil receptors, including Dectin-1 and TLR2. Molecular docking and analysis were performed by using UCSF Chimera, AutoDock Vina, Proteins.plus, and PyMol. In silico ADMET analysis was done by using the pkCSM web server. The result showed that both 1.6 and 0.9 kDa forms of 1, 3/1, 6 β-glucans oligosaccharides can bind with Dectin-1 and TLR2 better than the reference compounds. Their binding capacity with the whole molecule is better than with the known binding sites. The 1.6 kDa β-glucans bind to the macromolecules of TLR2 better than the 0.9 kDa ones. ADMET analyses suggest low absorption, very low blood–brain barrier permeability, no CYP2D6 metabolism, and no hepatotoxicity or genotoxicity. In conclusion, this study predicts that the fungal β-1, 3/1, 6-glucans oligosaccharides are low-toxic and are fecally excreted without metabolic transformation. Their binding to Dectin-1 and TLR2 receptors on neutrophils is stronger than that of reference compounds and is influenced by molecular weight. These findings suggest that they possess new binding sites to both receptors, warranting further studies.
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References
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