Bilastine Based Drugs as SARS-CoV-2 Protease Inhibitors: Molecular Docking, Dynamics, and ADMET Related Studies

IF 0.7 Q4 CHEMISTRY, MULTIDISCIPLINARY
A. Kumer, Unesco Chakma, M. Matin
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引用次数: 4

Abstract

Bilastine drugs, structurally piperidine-1-carboxylate and sulfonyloxyethyl carboxylate derivatives, have significantly been employed as the medication of second-generation antihistamine drugs, and are used for the treatment of allergic rhinoconjunctivities and urticarial (hives). The bilastine drugs, composed of benzene carboxylate, propanoate, carboxylate, methyl-sulfonate, propanoic acid, butanoic acid, and pentanoic acid derivatives, were investigated through computational tools against SARS-CoV-2. The COVID-19 virus consists of five proteases where the curial function is performed by main proteases (M-pro) and Spike proteases (S-pro). The M-pro and S-pro were selected for calculation of molecular docking by these bilastine drugs which showed higher binding energy (<-6.5 kcal/mol) for both proteases. The main carboxylic acid group in bilastine drugs is found the primary key for a high binding score to show the large binding affinity with M-pro and S-pro, and is highly responsible for forming the hydrogen bond although the various hydrophobic bonds were produced as a weak interaction. For justification, the stability of molecular docked ligand-protein complexes was investigated with molecular dynamics. It showed that the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of all these drugs were below the 0.9 angstrom after residue interaction. Moreover, the HOMO-LUMO gap, hardness, and softness provided full details for their chemical reactivity. In this view, the pharmacokinetics and Lipinski rule were calculated, and all of these molecules had satisfied the Lipinski rule. Finally, using the admetSAR online database, absorption, distribution, metabolism, excretion, and toxicity have been calculated which indicated that these bilastine drugs are non-carcinogenic and less harmful for both aquatic and non-aquatic species. [GRAPHICS]
以比拉斯汀为基础的药物作为严重急性呼吸系统综合征冠状病毒2型蛋白酶抑制剂:分子对接、动力学和ADMET相关研究
比拉斯汀类药物,结构上为哌啶-1-羧酸盐和磺酰氧基乙基羧酸盐衍生物,已被广泛用作第二代抗组胺药物,并用于治疗过敏性鼻结膜炎和荨麻疹。通过针对严重急性呼吸系统综合征冠状病毒2型的计算工具,研究了由苯羧酸盐、丙酸盐、羧酸盐、甲基磺酸盐、丙酸、丁酸和戊酸衍生物组成的双层药物。新冠肺炎病毒由五种蛋白酶组成,其中居里功能由主要蛋白酶(M-pro)和刺突蛋白酶(S-pro)执行。选择M-pro和S-pro来计算这些双层药物的分子对接,它们对两种蛋白酶都显示出更高的结合能(<-6.5 kcal/mol)。发现双层药物中的主要羧酸基团是高结合分数的主要关键,显示出与M-pro和S-pro的大结合亲和力,并且高度负责形成氢键,尽管各种疏水键是作为弱相互作用产生的。为了证明这一点,用分子动力学方法研究了分子对接配体-蛋白质复合物的稳定性。结果表明,在残基相互作用后,所有这些药物的均方根偏差(RMSD)和均方根波动(RMSF)均低于0.9埃。此外,HOMO-LUMO间隙、硬度和柔软度为其化学反应性提供了完整的细节。在此基础上,计算了药物动力学和利平斯基规则,所有这些分子都满足利平斯基法则。最后,使用admetSAR在线数据库计算了这些双肠药物的吸收、分布、代谢、排泄和毒性,表明这些药物对水生和非水生物种都是非致癌的,危害较小。[图形]
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来源期刊
Orbital: The Electronic Journal of Chemistry
Orbital: The Electronic Journal of Chemistry CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
1.10
自引率
0.00%
发文量
25
审稿时长
10 weeks
期刊介绍: Orbital: The Electronic Journal of Chemistry is a quarterly scientific journal published by the Institute of Chemistry of the Universidade Federal de Mato Grosso do Sul, Brazil. Original contributions (in English) are welcome, which focus on all areas of Chemistry and their interfaces with Pharmacy, Biology, and Physics. Neither authors nor readers have to pay fees. The journal has an editorial team of scientists drawn from regions throughout Brazil and world, ensuring high standards for the texts published. The following categories are available for contributions: 1. Full papers 2. Reviews 3. Papers on Education 4. History of Chemistry 5. Short communications 6. Technical notes 7. Letters to the Editor The Orbital journal also publishes a number of special issues in addition to the regular ones. The central objectives of Orbital are threefold: (i) to provide the general scientific community (at regional, Brazilian, and worldwide levels) with a formal channel for the communication and dissemination of the Chemistry-related literature output by publishing original papers based on solid research and by reporting contributions which further knowledge in the field; (ii) to provide the community with open, free access to the full content of the journal, and (iii) to constitute a valuable channel for the dissemination of Chemistry-related investigations.
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