School of Chemistry, University of Wollongong, Wollongong, 2522, Australia.
Faculty of Pharmacy, University of Medicine and Pharmacy at Hochiminh City, 41 Dinh Tien Hoang, District 1, Hochiminh, Vietnam.
Interdiscip Sci. 2018 Sep;10(3):515-524. doi: 10.1007/s12539-016-0209-0. Epub 2017 Mar 11.
The chikungunya virus (CHIKV) envelope glycoproteins are considered important potential targets for anti-CHIKV drug discovery due to their crucial roles in virus attachment and virus entry. In this study, using two available crystal structures of the immature and mature forms of envelope glycoproteins, virtual screenings based on blind dockings and focused dockings were carried out to identify potential binding pockets and hit compounds for the virus. The chemical library database of compounds, NCI Diversity Set II, was used in these docking studies. In addition to reproducing previously reported examples, new binding pockets were identified, e.g., Pocket 2 in the 3N40, and Pocket 2 and Pocket 3 in the 3N42. Convergences in conformational sampling in docking using AutoDock Vina were evaluated. An analysis of docking results was carried out to understand interactions of the envelope glycoproteins complexes. Some key residues for interactions, for example Gly91 and His230, are identified as possessing important roles in the fusion process.
基孔肯雅病毒（CHIKV）包膜糖蛋白被认为是抗 CHIKV 药物发现的重要潜在靶点，因为它们在病毒附着和病毒进入中起着至关重要的作用。在这项研究中，使用两种可用的包膜糖蛋白不成熟和成熟形式的晶体结构，进行了基于盲目对接和聚焦对接的虚拟筛选，以识别病毒的潜在结合口袋和命中化合物。在这些对接研究中使用了化合物的 NCI 多样性集 II 化学库数据库。除了重现先前报道的例子外，还确定了新的结合口袋，例如 3N40 中的口袋 2 和 3N42 中的口袋 2 和口袋 3。评估了使用 AutoDock Vina 进行对接时构象采样的收敛性。对对接结果进行了分析，以了解包膜糖蛋白复合物的相互作用。确定了一些关键的相互作用残基，例如 Gly91 和 His230，它们在融合过程中具有重要作用。
