Identification of natural compounds as SARS-CoV-2 inhibitors via molecular docking and molecular dynamic simulation.
Identification of natural compounds as SARS-CoV-2 inhibitors via molecular docking and molecular dynamic simulation.
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DOI：
10.3389/fmicb.2022.1095068
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发表时间：
2022
影响因子：
5.2
通讯作者：
Lai, Yanni
中科院分区：
文献类型：
--
作者：
Han, Tiantian;Luo, Ziqing;Ji, Lichun;Wu, Peng;Li, Geng;Liu, Xiaohong;Lai, Yanni
关键词：
碱基突变增加了Delta和Lambda毒株的传染性和传播性，并导致COVID-19大流行的严重程度。分子对接和分子动力学（MD）模拟经常用于药物发现和重新定位。来自中草药的小分子化合物对病毒具有抑制作用。因此，本研究使用计算机模拟来研究小分子化合物对S蛋白的影响以及它们与血管紧张素转换酶2（ACE 2）受体之间的结合。本研究采用分子对接、分子动力学模拟、蛋白质-蛋白质分析等方法，探讨了中草药植物化学物质对SARS-CoV-2的药物靶向抑制作用。针对SARS-CoV-2 Lambda和Delta突变体的S蛋白筛选了12，978种植物化学物质。分子对接结果表明，65.61%和65.28%的化合物与λ和δ突变体的S蛋白具有相对稳定的结合能力（对接得分≤-6）。与λ和δ突变体结合能最高的5个化合物是威灵仙甙AR 2（−9.7），atratoglaucoside，B（-9.5），酸浆苦素B（−9.5），阿曲苷，a（−9.4），Ochnaflavone（−9.3）和新白花醌a（−10），Wikstrosin（−9.7），xilingsaponin A（−9.6），ardisianoside G（−9.6）和23-epi-26-deoxyactein（−9.6）。分子动力学模拟结果表明，木麻黄素、异叶连翘苷D、原金丝桃素和Glansrin B分别与Lambda和Delta突变体的S蛋白突变位点相互作用，与穗蛋白形成能量稳定复合物的能力较好。此外，蛋白质-蛋白质对接进行了评估的ACE 2结合能力的变化所造成的四种植物化学品和S蛋白复合物的形成。分析表明，四种植物化学物质与S蛋白的结合，可以降低与ACE 2结合的稳定性，从而降低病毒的复制能力。综上所述，本研究得出结论，四种植物化学物质（木麻黄素、异叶金丝桃素D、原金丝桃素和Glansrin B）对SARS-CoV-2 S蛋白的结合位点具有显著影响。这项研究需要进一步的体外和体内实验验证这些主要的植物化学物质，以评估其潜在的抗SARS-CoV-2。
Base mutations increase the contagiousness and transmissibility of the Delta and Lambda strains and lead to the severity of the COVID-19 pandemic. Molecular docking and molecular dynamics (MD) simulations are frequently used for drug discovery and relocation. Small molecular compounds from Chinese herbs have an inhibitory effect on the virus. Therefore, this study used computational simulations to investigate the effects of small molecular compounds on the spike (S) protein and the binding between them and angiotensin-converting enzyme 2 (ACE2) receptors. In this study, molecular docking, MD simulation, and protein–protein analysis were used to explore the medicinal target inhibition of Chinese herbal medicinal plant chemicals on SARS-CoV-2. 12,978 phytochemicals were screened against S proteins of SARS-CoV-2 Lambda and Delta mutants. Molecular docking showed that 65.61% and 65.28% of the compounds had the relatively stable binding ability to the S protein of Lambda and Delta mutants (docking score ≤ −6). The top five compounds with binding energy with Lambda and Delta mutants were clematichinenoside AR2 (−9.7), atratoglaucoside,b (−9.5), physalin b (−9.5), atratoglaucoside, a (−9.4), Ochnaflavone (−9.3) and neo-przewaquinone a (−10), Wikstrosin (−9.7), xilingsaponin A (−9.6), ardisianoside G (−9.6), and 23-epi-26-deoxyactein (−9.6), respectively. Four compounds (Casuarictin, Heterophylliin D, Protohypericin, and Glansrin B) could interact with S protein mutation sites of Lambda and Delta mutants, respectively, and MD simulation results showed that four plant chemicals and spike protein have good energy stable complex formation ability. In addition, protein–protein docking was carried out to evaluate the changes in ACE2 binding ability caused by the formation of four plant chemicals and S protein complexes. The analysis showed that the binding of four plant chemicals to the S protein could reduce the stability of the binding to ACE2, thereby reducing the replication ability of the virus. To sum up, the study concluded that four phytochemicals (Casuarictin, Heterophylliin D, Protohypericin, and Glansrin B) had significant effects on the binding sites of the SARS-CoV-2 S protein. This study needs further in vitro and in vivo experimental validation of these major phytochemicals to assess their potential anti-SARS-CoV-2.
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DOI：
10.1016/s0140-6736(22)00462-7
发表时间：
2022-04-02
期刊：
Lancet (London, England)
影响因子：
--
作者：
Nyberg T;Ferguson NM;Nash SG;Webster HH;Flaxman S;Andrews N;Hinsley W;Bernal JL;Kall M;Bhatt S;Blomquist P;Zaidi A;Volz E;Aziz NA;Harman K;Funk S;Abbott S;COVID-19 Genomics UK (COG-UK) consortium;Hope R;Charlett A;Chand M;Ghani AC;Seaman SR;Dabrera G;De Angelis D;Presanis AM;Thelwall S
通讯作者：
Thelwall S
影响因子：
5.2
作者：
通讯作者：
--
影响因子：
8.8
作者：
Kimura I;Kosugi Y;Wu J;Zahradnik J;Yamasoba D;Butlertanaka EP;Tanaka YL;Uriu K;Liu Y;Morizako N;Shirakawa K;Kazuma Y;Nomura R;Horisawa Y;Tokunaga K;Ueno T;Takaori-Kondo A;Schreiber G;Arase H;Genotype to Phenotype Japan (G2P-Japan) Consortium;Motozono C;Saito A;Nakagawa S;Sato K
通讯作者：
Sato K
影响因子：
3.7
作者：
Chen K;Kurgan L
通讯作者：
Kurgan L
泛组学时代精准肿瘤学的个性化网络药物重新定位基础设施
影响因子：
9.5
作者：
Cheng, Feixiong;Hong, Huixiao;Wei, Yuquan
通讯作者：
Wei, Yuquan