Potential treatment with Chinese and Western medicine targeting NSP14 of SARS-CoV-2
Potential treatment with Chinese and Western medicine targeting NSP14 of SARS-CoV-2
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针对SARS-CoV-2 NSP14的中西医潜在治疗方法
DOI：
10.1016/j.jpha.2020.08.002
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发表时间：
2021-06-30
影响因子：
8.8
通讯作者：
Yang, Tai
中科院分区：
文献类型：
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作者：
Liu, Chao;Zhu, Xiaoxiao;Yang, Tai
由严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）疫情是严重的全球健康威胁。这就迫切需要开发对抗这种致命疾病的有效药物。携带RNA帽鸟嘌呤n7 -甲基转移酶和3‘-5’外核糖核酸酶活性的SARS-CoV-2非结构蛋白14 （NSP14）可能是潜在的药物干预靶点。SARS- cov -2的NSP14与SARS的NSP14 （PDB 5NFY）有98.7%的相似性。然后，以SARS NSP14 （PDB 5NFY）为模板，利用modelmodel9.18对SARS- cov -2 NSP14结构进行建模，进行虚拟筛选。根据AutoDock Vina1.1.2的对接评分，选择18种小分子药物进行进一步评价。基于5 ns MD仿真轨迹，采用MM/GBSA法计算了结合自由能（DG）。沙喹那韦、金丝桃素、黄芩苷和Bromocriptine在n端结合的自由能分别为-37.2711 +/- 3.2160、-30.1746 +/- 3.1914、-23.8953 +/- 4.4800和-34.1350 +/- 4.3683 kcal/mol，与c端结合的自由能分别为-60.2757 +/- 4.7708、-30.9955 +/- 2.9975、-46.3099 +/- 3.5689和-59.8104 +/- 3.5389 kcal/mol。因此，沙基那韦、金丝桃素、黄芩苷和溴隐亭等化合物可结合SARS-CoV-2 NSP14同源模型的n端和c端，为进一步研究提供了抗SARS-CoV-2的候选药物。(c) 2020年西安交通大学这是一篇基于CC by-nc-nd许可（http://creativecommons.org/licenses/by-nc-nd/4.0/）的开放获取文章。
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global health threat. This raises an urgent need for the development of effective drugs against the deadly disease. SARS-CoV-2 non-structural protein 14 (NSP14) carrying RNA cap guanine N7-methyltransferase and 3'-5' exoribonuclease activities could be a potential drug target for intervention. NSP14 of SARS-CoV-2 shares 98.7% of similarity with the one (PDB 5NFY) of acute respiratory syndrome (SARS) by ClustalW. Then, the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14 (PDB 5NFY) as template for virtual screening. Based on the docking score from AutoDock Vina1.1.2, 18 small molecule drugs were selected for further evaluation. Based on the 5 ns MD simulation trajectory, binding free energy (DG) was calculated by MM/GBSA method. The calculated binding free energies of Saquinavir, Hypericin, Baicalein and Bromocriptine for the N-terminus of the homology model were -37.2711 +/- 3.2160, -30.1746 +/- 3.1914, -23.8953 +/- 4.4800, and -34.1350 +/- 4.3683 kcal/mol, respectively, while the calculated binding free energies were -60.2757 +/- 4.7708, -30.9955 +/- 2.9975, -46.3099 +/- 3.5689, and -59.8104 +/- 3.5389 kcal/mol, respectively, when binding to the C-terminus. Thus, the compounds including Saquinavir, Hypericin, Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14, providing a candidate drug against SARS-CoV-2 for further study. (c) 2020 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).