Pharmacokinetics and Molecular Docking Studies of Uridine Derivatives as SARS-COV-2 Mpro Inhibitors

IF 1.4 Q3 CHEMISTRY, MULTIDISCIPLINARY
J. Maowa, Hosen, A. Alam, K. M. Rana, Y. Fujii, Y. Ozeki, S. Kawsar
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引用次数: 1

Abstract

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.
尿苷衍生物作为严重急性呼吸系统综合征冠状病毒2型Mpro抑制剂的药代动力学和分子对接研究
在本研究中,我们采用密度泛函理论(DFT)对尿苷及其酰化衍生物进行了优化。所有设计的衍生物都在B3LYP/3-21G理论水平上进行了优化。在随后的分析中,探讨了修饰衍生物的电荷分布、极化率和热力学性质,如自由能、热容和熵,以评估某些基团如何影响药物性质。为了了解结合模式和分子相互作用,进行了分子对接计算,通过筛选总共14种具有显著抗菌和抗真菌活性的衍生物,指出了严重急性呼吸系统综合征冠状病毒2型主要蛋白酶(PDB:6Y84和6LU7)的潜在抑制剂。据观察,所有衍生物在热力学上都更稳定,其中一些衍生物比其他衍生物更具化学反应性。这里研究的大多数化合物可以在主要蛋白酶的关键催化残基HIS41和CYS145附近结合,并且这些化合物被其他活性位点残基包围,如GLY143、MET49、MET165、GLY143,HIS163、PRO168、GLU166、GLN189和SER144。最后,对所有修饰的尿苷衍生物进行了硅ADMET和类药物性质的分析。我们的扩展计算和统计分析表明,这些选定的尿苷衍生物可能用作对抗严重急性呼吸系统综合征冠状病毒2型Mpro的潜在抑制剂。
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来源期刊
Physical Chemistry Research
Physical Chemistry Research CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
2.70
自引率
8.30%
发文量
18
期刊介绍: The motivation for this new journal is the tremendous increasing of useful articles in the field of Physical Chemistry and the related subjects in recent years, and the need of communication between Physical Chemists, Physicists and Biophysicists. We attempt to establish this fruitful communication and quick publication. High quality original papers in English dealing with experimental, theoretical and applied research related to physics and chemistry are welcomed. This journal accepts your report for publication as a regular article, review, and Letter. Review articles discussing specific areas of physical chemistry of current chemical or physical importance are also published. Subjects of Interest: Thermodynamics, Statistical Mechanics, Statistical Thermodynamics, Molecular Spectroscopy, Quantum Chemistry, Computational Chemistry, Physical Chemistry of Life Sciences, Surface Chemistry, Catalysis, Physical Chemistry of Electrochemistry, Kinetics, Nanochemistry and Nanophysics, Liquid Crystals, Ionic Liquid, Photochemistry, Experimental article of Physical chemistry. Mathematical Chemistry.
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