IEEE/ACM Trans Comput Biol Bioinform. 2020 Sep-Oct;17(5):1751-1761. doi: 10.1109/TCBB.2019.2911081. Epub 2019 Apr 15.
In-silico pipeline is applied for identifying and designing novel inhibitors against ZIKV NS1 protein. Comparative molecular docking studies are performed to explore the binding of structurally diverse compounds to ZIKV NS1 by AutoDock/Vina and GOLD. The Zika virus (ZIKV) is a flavivirus, responsible for life-threatening infections and transmitted by Aedes mosquitoes in other organisms. It is associated with Guillain Barre Syndrome (GBS) and microcephaly. This epidemic increase in GBS and microcephaly convoyed the World Health Organization to affirm ZIKV a public health crisis. To combat the ZIKV infections, non-structural protein 1 (NS1), a major host-interaction molecule contributing towards replication, pathogenesis and immune evasion is targeted in the current study. For this purpose, a comprehensive study is required to develop potential novel antiviral inhibitors. Three compounds were identified through docking programs exhibiting properties which are non-toxic to human host and could inhibit the elusive ZIKV. Significant interaction with active site residues and H-bond interactions with the key residues were analyzed for these compounds using molecular dynamics simulation. Free energy calculation predicted higher affinity of Deoxycalyxin-A for ZIKV NS1. This study contributes towards fighting ZIKV infections and can help researchers in designing drug for the treatment of ZIKV.
本文应用计算机模拟管道技术来识别和设计针对 Zika 病毒 NS1 蛋白的新型抑制剂。通过 AutoDock/Vina 和 GOLD 进行对比分子对接研究，探索结构多样的化合物与 Zika 病毒 NS1 的结合情况。 Zika 病毒（ZIKV）是黄病毒科的一种病毒，可导致危及生命的感染，并通过埃及伊蚊在其他生物体中传播。它与格林-巴利综合征（GBS）和小头畸形有关。这种寨卡病毒引起的 GBS 和小头畸形的流行促使世界卫生组织将其确认为公共卫生危机。为了对抗 ZIKV 感染，本研究以非结构蛋白 1（NS1）为靶点，该蛋白是一种主要的宿主相互作用分子，有助于复制、发病机制和免疫逃逸。为此，需要进行全面的研究来开发潜在的新型抗病毒抑制剂。通过对接程序鉴定了三种具有非毒性的化合物，这些化合物可能会抑制难以捉摸的 Zika 病毒。通过分子动力学模拟，对这些化合物与活性位点残基的显著相互作用和与关键残基的氢键相互作用进行了分析。自由能计算预测，Deoxycalyxin-A 与 Zika 病毒 NS1 的亲和力更高。本研究有助于对抗 Zika 病毒感染，并可以帮助研究人员设计治疗 Zika 病毒的药物。
