Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2.
Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2.
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DOI：
10.1038/s41598-020-74715-4
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发表时间：
2020-10-19
影响因子：
4.6
通讯作者：
Maulik U
中科院分区：
文献类型：
--
作者：
Basu A;Sarkar A;Maulik U
血管紧张素转换酶2（ACE 2）（EC：3.4.17.23）是一种跨膜蛋白，被认为是新型冠状病毒（SARS-CoV 2）刺突蛋白结合的受体。由于没有特定的药物可用于治疗COVID-19，因此设计新药非常重要和必要。在这方面，计算机模拟方法起着重要的作用，因为与使用实验研究的试错方法相比，它快速且具有成本效益。在目前令人担忧的情况下，天然产品是安全且易于获得的，可用于治疗冠状病毒感染的患者。本论文选择了五种黄酮类和蒽醌类植物化学物质作为小分子，对SARS-CoV 2刺突蛋白与其受体ACE 2分子进行了分子对接研究。分析了它们在刺突蛋白结合结构上与受体的分子结合位点。根据该分析，橙皮苷、大黄素和白杨素被选为来自印度和中国药用植物的有效天然产物，用于治疗COVID-19。其中橙皮苷能与ACE 2蛋白结合，并能与ACE 2蛋白结构和SARS-CoV 2刺突蛋白非竞争性结合。ACE 2蛋白与刺突蛋白和橙皮苷的结合位点位于ACE 2蛋白的不同部位。分子对接和分子动力学研究证实了配体刺突蛋白引起ACE 2蛋白三维构象的变化。该化合物调节ACE 2和刺突蛋白结合结构的结合能。该结果表明，由于橙皮苷的存在，ACE 2和刺突蛋白片段的结合结构变得不稳定。因此，这种天然产物可以在SARS CoV 2感染中赋予抗病毒活性。通过定量构效关系（QSAR）研究进一步验证了这五种天然化合物的抗病毒活性。
Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role, as it is rapid and cost effective compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus affected patients, in the present alarming situation. In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. Their molecular binding sites on spike protein bound structure with its receptor have been analyzed. From this analysis, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19. Among them, the phytochemical hesperidin can bind with ACE2 protein and bound structure of ACE2 protein and spike protein of SARS-CoV2 noncompetitively. The binding sites of ACE2 protein for spike protein and hesperidin, are located in different parts of ACE2 protein. Ligand spike protein causes conformational change in three-dimensional structure of protein ACE2, which is confirmed by molecular docking and molecular dynamics studies. This compound modulates the binding energy of bound structure of ACE2 and spike protein. This result indicates that due to presence of hesperidin, the bound structure of ACE2 and spike protein fragment becomes unstable. As a result, this natural product can impart antiviral activity in SARS CoV2 infection. The antiviral activity of these five natural compounds are further experimentally validated with QSAR study.
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影响因子：
14.8
作者：
Kozakov D;Hall DR;Xia B;Porter KA;Padhorny D;Yueh C;Beglov D;Vajda S
通讯作者：
Vajda S
影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
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Farzan M
影响因子：
7.6
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Ho TY;Wu SL;Chen JC;Li CC;Hsiang CY
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Hsiang CY
影响因子：
11.4
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Li, WH;Zhang, CS;Sui, JH;Kuhn, JH;Moore, MJ;Luo, SW;Wong, SK;Huang, IC;Xu, KM;Vasilieva, N;Murakami, A;He, YQ;Marasco, WA;Guan, Y;Choe, HY;Farzan, M
通讯作者：
Farzan, M
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE