Halim Sobia A, Khan Shanza, Khan Ajmal, Wadood Abdul, Mabood Fazal, Hussain Javid, Al-Harrasi Ahmed
Department of Biochemistry, Kinnaird College for Women, Lahore, Pakistan.
Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
Front Chem. 2017 Oct 31;5:88. doi: 10.3389/fchem.2017.00088. eCollection 2017.
Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database. The compounds matched with the pharmacophore model were docked into the active site of NS-3 helicase. Based on docking scores and binding interactions, 25 compounds are suggested to be potential inhibitors of NS3 Helicase. The pharmacokinetic properties of these hits were predicted. The selected hits revealed acceptable ADMET properties. This study identified potential inhibitors of NS-3 Helicase , and can be helpful in the treatment of Dengue.
登革热是一个新出现的公共卫生问题，每年有数百万人发生病毒感染，目前尚无有效的治疗方法。登革病毒（DENV）编码的非结构蛋白3（NS-3）解旋酶被认为是设计抗登革热新型有效药物的潜在药物靶点。解旋酶参与登革热RNA的解旋。本研究通过基于配体和结构的方法设计新型NS-3解旋酶抑制剂。首先生成基于配体的药效团模型，用于筛选从ZINC数据库收集的1201474种化合物。与药效团模型匹配的化合物被对接至NS-3解旋酶的活性位点。基于对接分数和结合相互作用，建议25种化合物为NS3解旋酶的潜在抑制剂。预测了这些命中化合物的药代动力学性质。所选命中化合物显示出可接受的ADMET性质。本研究鉴定出NS-3解旋酶的潜在抑制剂，有助于登革热的治疗。
