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依布硒啉与潜在的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)靶点的适宜相互作用:一种方法。

Ebselen suitably interacts with the potential SARS-CoV-2 targets: an approach.

作者信息

Sarkar Chandan, Abdalla Mohnad, Mondal Milon, Khalipha Abul Bashar Ripon, Ali Nasir

机构信息

Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh.

Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Shandong Province, PR China.

出版信息

J Biomol Struct Dyn. 2022;40(22):12286-12301. doi: 10.1080/07391102.2021.1971562. Epub 2021 Aug 30.

Abstract

Ebselen (SPI-1005) is an active selenoorganic compound that can be found potential inhibitory activity against different types of viral infections such as zika virus, influenza A virus, HCV, and HIV-1; and also be found to exhibit promising antiviral activity against SARS-CoV-2 in cell-based assays but its particular target action against specific non-structural and structural proteins of SARS-CoV-2 is unclear to date. The purpose of this study is to evaluate the anti-SARS-CoV-2 efficacy of Ebselen along with the determination of the specific target among the 12 most common target proteins of SARS-CoV-2. AutoDock Vina in PyRx platform was used for docking analysis against the 12 selected SARS-CoV-2 encoded drug targets. ADME profiling was examined by using SwissADME online server. The stability of binding mode in the target active sites was evaluated using molecular dynamics (MD) simulation studies through NAMD and Desmond package software application. In this docking study, we recognized that Ebselen possesses the highest affinity to N protein (C domain) (PDB ID: 6YUN) and PLpro (PDB ID: 6WUU) among the selected SARS-CoV-2 targets showing -7.4 kcal/mol binding energy. The stability of Ebselen-6YUN and Ebselen-6WUU was determined by a 100 ns trajectory of all-atom molecular dynamics simulation. Structural conformation of these two complexes displayed stable root mean square deviation (RMSD), while root mean square fluctuations (RMSF) were also found to be consistent. This molecular docking study may propose the efficiency of Ebselen against SARS-CoV-2 to a significant extent which makes it a candidature of COVID-19 treatment.

摘要

依布硒啉(SPI-1005)是一种活性有机硒化合物,对寨卡病毒、甲型流感病毒、丙型肝炎病毒和HIV-1等不同类型的病毒感染具有潜在抑制活性;在基于细胞的试验中还发现其对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)具有良好的抗病毒活性,但迄今为止,其针对SARS-CoV-2特定非结构蛋白和结构蛋白的具体靶向作用尚不清楚。本研究的目的是评估依布硒啉对SARS-CoV-2的抗病毒效果,并确定其在SARS-CoV-2的12种最常见靶蛋白中的具体靶点。使用PyRx平台中的AutoDock Vina对选定的12种SARS-CoV-2编码药物靶点进行对接分析。通过使用SwissADME在线服务器检查药物代谢动力学特征。通过NAMD和Desmond软件包应用分子动力学(MD)模拟研究评估靶标活性位点结合模式的稳定性。在这项对接研究中,我们发现在选定的SARS-CoV-2靶点中,依布硒啉对N蛋白(C结构域)(PDB ID:6YUN)和木瓜蛋白酶样蛋白酶(PLpro)(PDB ID:6WUU)具有最高亲和力,结合能为-7.4千卡/摩尔。通过100纳秒的全原子分子动力学模拟轨迹确定依布硒啉-6YUN和依布硒啉-6WUU的稳定性。这两种复合物的结构构象显示出稳定的均方根偏差(RMSD),同时均方根波动(RMSF)也被发现是一致的。这项分子对接研究在很大程度上可能表明依布硒啉对SARS-CoV-2的有效性,这使其成为治疗2019冠状病毒病的候选药物。

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