In-Silico Molecular Docking, Validation, Drug-Likeness, and ADMET Studies of Antiandrogens to Use in the Fight against SARS-CoV-2

IF 1.4 Q3 CHEMISTRY, MULTIDISCIPLINARY

Physical Chemistry Research Pub Date : 2022-01-01 DOI:10.22036/PCR.2022.324549.2016

A. Saih, E. Imane, H. Baba, M. Bouqdayr, H. Ghazal, S. Hamdi, S. Moussamih, H. Bennani, R. Saile, A. Kettani, L. Wakrim

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引用次数: 1

Abstract

The SARS-CoV-2 is the novel coronavirus that causes the pandemic COVID-19, which has originated in Wuhan, China, in December 2019. Early studies have generally shown that human Angiotensin-Converting Enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are responsible for the viral entry of SARS-CoV-2 into target cells. TMPRSS2 as androgen-regulated is highly expressed in the prostate and other tissues including the lung. We investigated the interaction between the TMPRSS2 protein and selected antiandrogens, namely bicalutamide, enzalutamide, apalutamide, flutamide, nilutamide, and darolutamide using in-silico molecular docking. The results showed that apalutamide (-8.8 Kcal mol-1) and bicalutamide (-8.6 Kcal mol-1) had the highest docking score. The molecular docking process was validated by re-docking the peptide-like-inhibitor-serine protease hepsin and superimposing them onto the reference complex. Last of all, the tested compounds have been evaluated for their pharmacokinetic and drug-likeness properties and concluded that these compounds except nilutamide (mutagenic) can be granted as potential inhibitors of SARS-CoV-2. This in-silico study result encourages its use as means for drug discovery of new COVID-19 treatment. © 2023. Physical Chemistry Research. All Rights Reserved.

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抗雄激素在抗击SARS-CoV-2中的分子对接、验证、药物相似性和ADMET研究

SARS-CoV-2是导致2019年12月起源于中国武汉的COVID-19大流行的新型冠状病毒。早期研究普遍表明，人血管紧张素转换酶2 (ACE2)和跨膜蛋白酶丝氨酸2 (TMPRSS2)是SARS-CoV-2病毒进入靶细胞的原因。雄激素调控的TMPRSS2在前列腺及包括肺在内的其他组织中高表达。我们利用硅基分子对接技术研究了TMPRSS2蛋白与抗雄激素(比卡鲁胺、恩杂鲁胺、阿帕鲁胺、氟他胺、尼鲁胺和达罗他胺)的相互作用。结果表明，阿帕鲁胺(-8.8 Kcal mol-1)和比卡鲁胺(-8.6 Kcal mol-1)的对接评分最高。通过将肽样抑制剂-丝氨酸蛋白酶hepsin重新对接并叠加到参比复合物上，验证了分子对接过程。最后，对测试化合物的药代动力学和药物相似性进行了评估，并得出结论，除尼鲁胺(诱变)外，这些化合物可被授予作为SARS-CoV-2的潜在抑制剂。这一计算机研究结果鼓励将其用作新型COVID-19治疗药物发现的手段。©2023。物理化学研究。版权所有。

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来源期刊

Physical Chemistry Research CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

2.70

自引率

8.30%

发文量

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.