Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors
Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors
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DOI：
10.1016/j.compbiolchem.2020.107325
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发表时间：
2020-10-01
影响因子：
3.1
通讯作者：
Castelan-Vega, Juan A.
中科院分区：
文献类型：
--
作者：
Jimenez-Alberto, Alicia;Maria Ribas-Aparicio, Rosa;Castelan-Vega, Juan A.
COVID-19引起的全球紧急情况使发现能够抑制SARS-CoV-2的药物成为优先事项，以降低这种疾病的死亡率和发病率。重新使用已批准的药物可以提供替代药物，因为它们有记录的安全记录以及大规模生产的基础设施，因此可以迅速和充分覆盖。SARS-CoV-2的主要蛋白酶（Mpro）是一个很好的治疗靶点，因为它对病毒复制至关重要;然而，Mpro具有高度灵活的活性位点，在进行计算机辅助药物发现时必须考虑。在这项工作中，潜在的抑制剂的主要蛋白酶（Mpro的SARS冠状病毒-2的）通过对接辅助虚拟筛选程序进行了鉴定。总共有4384种药物，所有批准用于人类使用，对Mpro的三个构象进行了筛选。通过分子动力学模拟和结合自由能分析对配体进行了进一步的研究。目前共有9种分子被批准作为SARS-CoV-2的潜在抑制剂。这些分子可以进一步测试，以加速抗COVID-19疗法的开发。
The global emergency caused by COVID-19 makes the discovery of drugs capable of inhibiting SARS-CoV-2 a priority, to reduce the mortality and morbidity of this disease. Repurposing approved drugs can provide ther-apeutic alternatives that promise rapid and ample coverage because they have a documented safety record, as well as infrastructure for large-scale production. The main protease of SARS-CoV-2 (Mpro) is an excellent therapeutic target because it is critical for viral replication; however, Mpro has a highly flexible active site that must be considered when performing computer-assisted drug discovery. In this work, potential inhibitors of the main protease (Mpro) of SARS-Cov-2 were identified through a docking-assisted virtual screening procedure. A total of 4384 drugs, all approved for human use, were screened against three conformers of Mpro. The ligands were further studied through molecular dynamics simulations and binding free energy analysis. A total of nine currently approved molecules are proposed as potential inhibitors of SARS-CoV-2. These molecules can be further tested to speed the development of therapeutics against COVID-19.