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登革病毒（Dengue virus, DENV）是全球流行范围最广、疾病负担最重的虫媒病毒，目前临床仍缺乏安全有效的抗病毒治疗方法。DENV非结构蛋白NS2B-NS3蛋白酶（NS2B-NS3pro）在病毒多聚蛋白加工和免疫逃逸中发挥关键作用，是抗DENV药物研发的核心靶点。当前，NS2B-NS3pro抑制剂的开发策略已呈多元化态势：结构指导的策略凭借对NS2B-NS3pro构象特征及动态变化的深入解析，为正构/别构抑制剂的理性设计与虚拟筛选提供了关键依据；而经验驱动与高通量筛选则拓宽了先导化合物的来源。然而，现有研究虽在先导分子发现和机制理解上取得显著进展，但其临床转化仍受制于化合物稳定性、成药性及体内有效性等瓶颈。本文综述了近年来在NS2BNS3pro抑制剂开发方面的最新进展，并对整合结构生物学、计算化学与宿主靶点研究的未来趋势进行展望，旨在为高效、安全的抗DENV药物开发提供参考。
Abstract：Dengue virus(DENV) is one of the most widespread arboviral pathogens worldwide and imposes a substantial global disease burden, yet safe and effective antiviral therapies remain lacking. The DENV nonstructural NS2B– NS3 protease(NS2B– NS3 pro) plays a central role in viral polyprotein processing and immune evasion, making it a key target for antiviral drug development. In recent years, strategies for developing NS2B – NS3 pro inhibitors have become increasingly diverse. Structure-based approaches, enabled by detailed insights into the conformational features and dynamic behavior of NS2 B–NS3 pro, have provided a strong foundation for the rational design and virtual screening of both orthosteric and allosteric inhibitors. Meanwhile, empirical approaches and high-throughput screening have expanded the repertoire of potential lead compounds. Despite significant progress in lead discovery and mechanistic understanding, clinical translation remains constrained by challenges related to compound stability, druggability, and in vivo efficacy. This review summarizes recent advances in NS2 B–NS3 pro inhibitor development and highlights future directions involving the integration of structural biology, computational chemistry, and host-targeted strategies, with the aim of facilitating the development of potent and safe anti-dengue therapeutics.
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DOI：10.13242/j.cnki.bingduxuebao.260073
中图分类号:R91
引用信息:
[1]朱浩嘉,邱丰,曹鹏,等.登革病毒NS2B-NS3pro抑制剂的研究进展[J].病毒学报,2026,42(03):1012-1021.DOI:10.13242/j.cnki.bingduxuebao.260073.
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