A Challenge for Uridine Derivatives as Inhibitors against SARS-COV-2 Main Protease | Chapter 2 | New Advances in Medicine and Medical Science Vol. 4

 This study is met on the identification of uridine descendants with the aim of assisting the identification of specific drugs for the situation of COVID-19. Nucleoside derivatives very contribute to drug and clinical fields as curative agents. Various dispassionate trials are currently ongoing to identify distinguishing drugs for the treatment of novel all-encompassing threat viruses. The main protease of SARS-CoV-2 is a important target for the design and amplification of antiviral drugs. In this analysis, we optimized a nucleoside, uridine, and few of its acylated descendants (2-14) by employing bulk functional hypothesis (DFT) at the B3LYP/3-21G level of theory. In the following analysis, the charge allocation, polarizability, and thermodynamic properties in the way that free energy, heat volume, and entropy of reduced compounds were investigated to decide how certain groups (aliphatic and perfumed) influence drug properties. All descendants were found expected thermodynamically more stable than the person ligand uridine, with few being more chemically reactive than others. To examine drug interactions accompanying receptor proteins, molecular mooring methods are ultimate suitable tools. The blind mooring method engages a search throughout all surface of the protein molecule for binding sites. Then, microscopic docking was acted against the SARS-CoV-2 main protease (PDB: 6Y84 and 6LU7) to investigate the binding mode(s) and binding affinities of the picked uridine derivatives. In the study, thirteen uridine derivatives accompanying different aliphatic and scented chains (2–14) were designed, and a quantity chemical study was performed to decide their thermochemical properties. Most of the compounds intentional here take care of bind near the important catalytic residues, HIS41, and CYS145 of the main protease and were surrounded by added active site residues, in the way that GLY143, MET49, MET165, HIS163, PRO168, GLU166, GLN189, and SER144. Significant binding affinities (-6.0 to -7.8 kcal/mol) for 6LU7 and (-5.9 to -7.7 kcal/mol) for 6Y84 were found, that revealed the effectiveness of inhibition of uridine products against SARS-CoV-2 Mpro. It was resolved that most of the selected uridine descendants show promising endeavors and could be used to design active antiviral drugs against SARS-CoV-2. Finally, all the modified uridine products were analyzed in silico for ADMET and drug-like characteristics. Overall, the present study might be questioning and helpful for the incident of novel uridine-based potential inhibitors against SARS-CoV-2 Mpro.

Author(s) Details:

Sarkar M. A. Kawsar,
Department of Chemistry, Faculty of Science, Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), University of Chittagong, Chittagong-4331, Bangladesh.

Please see the link here: https://stm.bookpi.org/NAMMS-V4/article/view/10705