Abstract：
Dengue fever (DF) is an endemic disease that has become a public health concern around the globe. The NS3 protease-helicase enzyme is an important target for the development of antiviral drugs against DENV (dengue virus) due to its impact on viral replication. Inhibition of the activity of the NS3 protease-helicase enzyme complex significantly inhibits the infection associated with DENV. Unfortunately, there are no scientifically approved antiviral drugs for its prevention. However, this study has been developed to find natural bioactive molecules that can block the activity of the NS3 protease-helicase enzyme complex associated with DENV infection through molecular docking, MM-GBSA (molecular mechanics-generalized born surface area), and molecular dynamics (MD) simulations. Three hundred forty-two (342) compounds selected from twenty traditional medicinal plants were retrieved and screened against the NS3 protease-helicase protein by molecular docking and MM-GBSA studies, where the top six phytochemicals have been identified based on binding affinities. The six compounds were then subjected to pharmacokinetics and toxicity analysis, and we conducted molecular dynamics simulations on three protein-ligand complexes to validate their stability. Through computational analysis, this study revealed the potential of the two selected natural bioactive inhibitors (CID-440015 and CID-7424) as novel anti-dengue agents.
摘要：
登革热（DF）是一种地方病，已成为全球公共卫生问题。由于NS3蛋白酶-解旋酶对病毒复制的影响，因此它是开发针对DENV（登革病毒）的抗病毒药物的重要靶标。抑制NS3蛋白酶-解旋酶复合物的活性显著抑制与DENV相关的感染。不幸的是,没有科学批准的抗病毒药物来预防它。然而,这项研究已经开发出天然的生物活性分子，可以通过分子对接阻断与DENV感染相关的NS3蛋白酶-解旋酶复合物的活性，MM-GBSA(分子力学-广义出生表面积)，和分子动力学(MD)模拟。通过分子对接和MM-GBSA研究，从20种传统药用植物中选择了三百四十二（342）种化合物，并针对NS3蛋白酶-解旋酶蛋白进行了筛选。根据结合亲和力确定了前六种植物化学物质。然后对六种化合物进行药代动力学和毒性分析，我们对三种蛋白质-配体复合物进行了分子动力学模拟，以验证其稳定性。通过计算分析,这项研究揭示了两种选定的天然生物活性抑制剂(CID-440015和CID-7424)作为新型抗登革热药物的潜力.
