PDF(Pubmed)
Abstract：
Microcephaly, Guillain-Barré syndrome, and potential sexual transmission stand as prominent complications associated with Zika virus (ZIKV) infection. The absence of FDA-approved drugs or vaccines presents a substantial obstacle in combatting the virus. Furthermore, the inclusion of pregnancy in the pharmacological screening process complicates and extends the endeavor to ensure molecular safety and minimal toxicity. Given its pivotal role in viral assembly and maturation, the NS2B-NS3 viral protease emerges as a promising therapeutic target against ZIKV. In this context, a dipeptide inhibitor was specifically chosen as a control against 200 compounds for docking analysis. Subsequent molecular dynamics simulations extending over 200 ns were conducted to ascertain the stability of the docked complex and confirm the binding of the inhibitor at the protein\'s active site. The simulation outcomes exhibited conformity to acceptable thresholds, encompassing parameters such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), ligand-protein interaction analysis, ligand characterization, and surface area analysis. Notably, analysis of ligand angles bolstered the identification of prospective ligands capable of inhibiting viral protein activity and impeding virus dissemination. In this study, the integration of molecular docking and dynamics simulations has pinpointed the dipeptide inhibitor as a potential candidate ligand against ZIKV protease, thereby offering promise for therapeutic intervention against the virus.
摘要：
小头畸形,格林-巴利综合征,潜在的性传播是与寨卡病毒（ZIKV）感染相关的突出并发症。缺乏FDA批准的药物或疫苗在对抗病毒方面存在重大障碍。此外，在药理学筛选过程中纳入妊娠会使确保分子安全性和最小毒性的努力复杂化并扩展。鉴于其在病毒组装和成熟中的关键作用，NS2B-NS3病毒蛋白酶成为抗ZIKV的有希望的治疗靶点。在这种情况下，特别选择二肽抑制剂作为针对200种化合物的对照用于对接分析。随后进行超过200ns的分子动力学模拟以确定对接复合物的稳定性并确认抑制剂在蛋白质活性位点的结合。模拟结果显示符合可接受的阈值，包括参数，如均方根偏差(RMSD)，均方根波动(RMSF)，配体-蛋白质相互作用分析，配体表征,和表面积分析。值得注意的是,配体角度的分析支持了能够抑制病毒蛋白活性和阻止病毒传播的预期配体的鉴定。在这项研究中,分子对接和动力学模拟的整合已经确定了二肽抑制剂作为抗ZIKV蛋白酶的潜在候选配体，从而为病毒的治疗干预提供了希望。
