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首页> 外文期刊>International Journal of Medical Sciences >Identification of Novel Compounds against an R294K Substitution of Influenza A (H7N9) Virus Using Ensemble Based Drug Virtual Screening
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Identification of Novel Compounds against an R294K Substitution of Influenza A (H7N9) Virus Using Ensemble Based Drug Virtual Screening

机译：使用基于集合的药物虚拟筛选鉴定针对甲型流感病毒（H7N9）R294K替代的新型化合物

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Influenza virus H7N9 foremost emerged in China in 2013 and killed hundreds of people in Asia since they possessed all mutations that enable them to resist to all existing influenza drugs, resulting in high mortality to human. In the effort to identify novel inhibitors combat resistant strains of influenza virus H7N9; we performed virtual screening targeting the Neuraminidase (NA) protein against natural compounds of traditional Chinese medicine database (TCM) and ZINC natural products. Compounds expressed high binding affinity to the target protein was then evaluated for molecular properties to determine drug-like molecules. 4 compounds showed their binding energy less than -11Kcal/mol were selected for molecular dynamics (MD) simulation to capture intermolecular interactions of ligand-protein complexes. The molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method was utilized to estimate binding free energy of the complex. In term of stability, NA-7181 (IUPAC namely {9-Hydroxy-10-[3-(trifluoromrthyl) cyclohexyl]-4.8-diazatricyclo [6.4.0.02,6]dodec-4-yl}(perhydro-1H-inden-5-yl)formaldehyde) achieved stable conformation after 20ns and 27ns for ligand and protein root mean square deviation, respectively. In term of binding free energy, 7181 gave the negative value of -30.031 (KJ/mol) indicating the compound obtained a favourable state in the active site of the protein.
机译：H7N9流感病毒最先在中国出现，并于2013年在亚洲杀死了数百人，因为他们拥有使他们能够抵抗所有现有流感药物的所有突变，导致人类高死亡率。为了确定新的抑制剂，对抗流感病毒H7N9的耐药株;我们针对神经氨酸酶（NA）蛋白针对传统中药数据库（TCM）和ZINC天然产物的天然化合物进行了虚拟筛选。然后评估对靶蛋白表达高结合亲和力的化合物的分子特性，以确定药物样分子。有4种化合物的结合能小于-11Kcal / mol，被选择用于分子动力学（MD）模拟以捕获配体-蛋白质复合物的分子间相互作用。分子力学/泊松玻尔兹曼表面积（MM / PBSA）方法用于估计复合物的结合自由能。就稳定性而言，NA-7181（IUPAC即{9-羟基-10- [3-（三氟甲基）环己基] -4.8-二氮三环[6.4.0.02,6]十二烷基-4-基}（全氢-1H-茚满- 5-基）甲醛在20ns和27ns后分别获得了稳定的构象，分别针对配体和蛋白质的均方根偏差。就结合自由能而言，7181的负值为-30.031（KJ / mol），表明该化合物在蛋白质的活性位点获得了良好的状态。

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