Voss Saan, Nitsche Christoph
Research School of Chemistry, Australian National University Canberra ACT 2601 Australia
RSC Med Chem. 2021 May 26;12(8):1262-1272. doi: 10.1039/d1md00080b. eCollection 2021 Aug 18.
West Nile virus infections can cause severe neurological symptoms. During the last 25 years, cases have been reported in Asia, North America, Africa, Europe and Australia (Kunjin). No West Nile virus vaccines or specific antiviral therapies are available to date. Various viral proteins and host-cell factors have been evaluated as potential drug targets. The viral protease NS2B-NS3 is among the most promising viral targets. It releases viral proteins from a non-functional polyprotein precursor, making it a critical factor of viral replication. Despite strong efforts, no protease inhibitors have reached clinical trials yet. Substrate-derived peptidomimetics have facilitated structural elucidations of the active protease state, while alternative compounds with increased drug-likeness have recently expanded drug discovery efforts beyond the active site.
西尼罗河病毒感染可导致严重的神经症状。在过去25年中，亚洲、北美、非洲、欧洲和澳大利亚（昆金病毒）均有病例报告。迄今为止，尚无西尼罗河病毒疫苗或特异性抗病毒疗法。多种病毒蛋白和宿主细胞因子已被评估为潜在的药物靶点。病毒蛋白酶NS2B-NS3是最有前景的病毒靶点之一。它从无功能的多蛋白前体中释放病毒蛋白，使其成为病毒复制的关键因素。尽管付出了巨大努力，但尚无蛋白酶抑制剂进入临床试验阶段。底物衍生的拟肽促进了活性蛋白酶状态的结构解析，而具有更高药物相似性的替代化合物最近已将药物研发工作扩展到活性位点之外。
