Document Type : Regular Article
Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh
Laboratory of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh
Laboratory of Functional Morphology, Graduate School of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan
Laboratory of Glycobiology and Marine Biochemistry, Department of Life and Environmental System Science, Graduate School of NanoBiosciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh
In this investigation, we have optimized uridine and its acylated derivatives employing density functional theory (DFT). All designed derivatives were optimized at the B3LYP/3-21G level of theory. Charge distribution, polarizability, and thermodynamic properties such as free energy, heat capacity, and entropy of modified derivatives were explored in the subsequent analysis to evaluate how certain groups impact the drug properties. To understand the mode of binding and molecular interaction, molecular docking calculation was carried out to point out the potential inhibitors of the SARS-CoV-2 main protease (PDB: 6Y84 and 6LU7) by screening a total of fourteen derivatives which exhibited significant antibacterial and antifungal activities. It was observed that all derivatives were thermodynamically more stable and some of them were more chemically reactive than others. Most of the compounds, studied out here could bind near the crucial catalytic residues, HIS41, and CYS145 of the main protease, and the compounds were surrounded by other active site residues like GLY143, MET49, MET165, GLY143, HIS163, PRO168, GLU166, GLN189, and SER144. Finally, all the modified uridine derivatives were analyzed in silico ADMET and drug-like properties. Our patulous computational and statistical analysis showed that these selected uridine derivatives may use as potential inhibitors against the SARS-CoV-2 Mpro.