The 2015 Zika outbreak sparked major global concern and emphasized the reality and dangers still posed by mosquito borne pathogens. While efforts have been made to develop a vaccine and other therapeutics, there is still a great demand for antiviral drugs targeting Zika and other flaviviruses. The non-structural protein 3 (NS3) helicase is a vital component of the viral replication complex, tasked with unwinding the viral dsRNA molecule into single strands. Given this critical function, the Zika virus helicase is a potential therapeutic target and the focus of many ongoing research efforts. Using a combination of drug docking and molecular dynamics simulations, we have identified a list of competitive helicase inhibitors targeting the ATP hydrolysis site and have discovered a potential allosteric site capable of distorting both of the protein's active sites.

2015 年寨卡病毒爆发引发了全球关注，并强调了蚊媒病原体仍然存在的现实和危险。尽管已经努力开发疫苗和其他疗法，但对针对寨卡病毒和其他黄病毒的抗病毒药物仍有很大需求。非结构蛋白 3 (NS3) 解旋酶是病毒复制复合体的重要组成部分，其任务是将病毒 dsRNA 分子解旋成单链。鉴于这一关键功能，寨卡病毒解旋酶是一个潜在的治疗目标，也是许多正在进行的研究工作的重点。结合药物对接和分子动力学模拟，我们确定了一系列针对 ATP 水解位点的竞争性解旋酶抑制剂，并发现了一个能够扭曲这两种蛋白质的潜在变构位点。