Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes
Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes
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DOI：
10.1080/07391102.2020.1758791
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发表时间：
2020-04-24
影响因子：
4.4
通讯作者：
Yelekci, Kemal
中科院分区：
文献类型：
--
作者：
Elmezayen, Ammar D.;Al-Obaidi, Anas;Yelekci, Kemal
于二零一九年十二月，中国武汉出现COVID-19疫情，感染广泛蔓延，影响数十万人。在此，努力鉴定市售药物，以便通过基于结构的虚拟筛选的手段将它们重新用于对抗冠状病毒。此外，ZINC 15文库被用于鉴定针对主要蛋白酶的新的先导物。首先使用同源建模方法生成人TMPRSS 2 3D结构。我们的分子对接研究显示了四种针对Mpro酶的潜在抑制剂，两种可用药物（他氨苄西林和鲁拉西酮）和两种新型药物样化合物（ZINC 00000702323和ZINC 000012481889）。此外，针对TMPRSS 2鉴定了四种有希望的抑制剂;鲁比替康和Loprazolam药物，以及化合物ZINC 000015988935和ZINC 000103558522。ADMET图谱显示，我们研究的命中物是安全的药物样化合物。此外，分子动力学（MD）模拟和结合自由能的计算使用MM-PBSA方法进行计算排名靠前的药物的相互作用能。作者：Ramaswamy H. Sarma
In December 2019, COVID-19 epidemic was described in Wuhan, China, and the infection has spread widely affecting hundreds of thousands. Herein, an effort was made to identify commercially available drugs in order to repurpose them against coronavirus by the means of structure-based virtual screening. In addition, ZINC15 library was used to identify novel leads against main proteases. Human TMPRSS2 3D structure was first generated using homology modeling approach. Our molecular docking study showed four potential inhibitors against Mpro enzyme, two available drugs (Talampicillin and Lurasidone) and two novel drug-like compounds (ZINC000000702323 and ZINC000012481889). Moreover, four promising inhibitors were identified against TMPRSS2; Rubitecan and Loprazolam drugs, and compounds ZINC000015988935 and ZINC000103558522. ADMET profile showed that the hits from our study are safe and drug-like compounds. Furthermore, molecular dynamic (MD) simulation and binding free energy calculation using the MM-PBSA method was performed to calculate the interaction energy of the top-ranked drugs. Communicated by Ramaswamy H. Sarma