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首页> 外文会议>International Symposium on Current Progress in Mathematics and Sciences >Fragment-based drug design of host endoplasmic reticulum α-glucosidase II inhibitors for dengue fever treatment using an integrated computational approach
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Fragment-based drug design of host endoplasmic reticulum α-glucosidase II inhibitors for dengue fever treatment using an integrated computational approach

机译：基于片段的宿主内质网的药物设计α-葡萄糖蛋白II抑制剂，用于使用综合计算方法进行登革热治疗

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Indonesia is one of many tropical countries that have a high prevalence of four different serotypes of dengue virus (DENV). DENV infection may cause dengue hemorrhagic fever (DHF) and eventually lead to the death. The latest report shows that the number of DHF incidences in Indonesia was increased rapidly from 1968 to 2013. Therefore, an effective treatment is needed to medicate and repress the mortality rate from infection. The inhibition of host endoplasmic reticulum α-glucosidase II (α-Glu II) could be a potential approach for the treatment of all DENV serotypes infection. An inhibitor that is targeting the α-Glu II can be designed by using computational fragment-based approach. In this research, we constructed Tanimoto-based on 1-deoxynojirimycin (DNJ) fragment similarity and in vitro fragment libraries. The ligand for α-Glu II inhibitors were designed by linking two potential fragments from these libraries. The result from molecular docking simulation showed that the ligand VG4 is the best inhibitor. Moreover, the simulation also showed the other seven ligands that designed in this research have a good binding affinity toward α-Glu II as well. Finally, computational pharmacological prediction and synthetic accessibility score also indicated the ligand VG4 and the selected ligands are potential to be developed as drug candidates for dengue therapeutics.
机译：印度尼西亚是众多热带国家之一，具有高血清术的热带国家之一，丹尾病毒（DENV）的四种不同血清型。 Denv感染可能导致登革热出血热（DHF）并最终导致死亡。最新报告显示，印度尼西亚的DHF事件数量从1968年到2013年迅速增加。因此，需要有效治疗治疗和压制感染的死亡率。抑制宿主内质网α-葡糖苷酶II（α-Glu II）可能是治疗所有Denv血清型感染的潜在方法。可以通过使用基于计算片段的方法来设计靶向α-Glu II的抑制剂。在这项研究中，我们构建了基于1-脱氧基尼霉素（DNJ）片段相似性和体外片段文库的Tanimoto。通过将来自这些文库的两个潜在片段连接到α-Glu II抑制剂的配体。来自分子对接模拟的结果表明，配体VG4是最佳抑制剂。此外，模拟还显示出在该研究中设计的其他七种配体，以及对α-Glu II的良好结合亲和力。最后，计算药理学预测和合成辅助性评分还表明了配体VG4，并且所选择的配体是作为登革热治疗剂的药物候选的潜力。

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