The computational screening of inhibitor for black fungus and white fungus by D-glucofuranose derivatives using in silico and SAR study

Abstract

Black fungus is the foremost life-threatening disease during the SARS-CoV-2 affected patients and spreading quickly in the region of the subcontinent of India although there was no prescribed proper medication. As the D-glucofuranose and its derivatives are reported to show strong antifungal activity, this study has been designed with them for their computational investigation. Firstly, the overall prediction of activity spectra for substances (PASS) value illustrates a good probability to be active(Pa) and probability to be inactive (Pi) value. Next, pharmacokinetics parameters including drug-likeness and Lipinski's rules, absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and overall quantum calculation of computational approaches by Density Functional Theory (DFT) have gradually been performed to analyze quantum calculations. After the analysis of docking score, it is found at -9.4 kcal/mol, -7.5 kcal/mol, -7.8 kcal/mol, -8.5 kcal/mol against the strain of black fungus protein strains Mycolicibacterium smegmatis, Mucor lusitanicus, Rhizomucor mien, and white fungus protein Candida Auris, Aspergillus luchuensis and Candida albicans. Next, the molecular dynamics of docked complexes have been performed to check their stability in biological systems with water ranging 100 ns calculating the Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) where the minimum RMSD and RMSF value indicated the higher stable configuration of docked complexes. These compounds have perfectly matched all the pharmacokinetics criteria to be a good drug candidate against both black and white fungus, and they are non-carcinogenic, low solubility, low toxic for both aquatic and non-aquatic. In addition, the quantum calculation using DFT conveys the strongest support and information about their chemical stability and biological significance. Finally, it could be concluded that the carboxylic group and methyl group in the benzene ring causes higher binding affinity against black and white fungus protein strain through the formation of hydrogen and hydrophobic bonds.