用于黄病毒感染的广谱药物：登革热、寨卡病毒及其他。
Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond.
作者信息
Boldescu Veaceslav, Behnam Mira A M, Vasilakis Nikos, Klein Christian D
机构信息
Medicinal Chemistry, Institute of Pharmacy and Molecular Biotechnology IPMB, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
Laboratory of Organic Synthesis and Biopharmaceuticals, Institute of Chemistry of the Academy of Sciences of Moldova, Academiei 3, 2028 Chisinau, Moldova.
出版信息
Nat Rev Drug Discov. 2017 Aug;16(8):565-586. doi: 10.1038/nrd.2017.33. Epub 2017 May 5.
Infections with flaviviruses, such as dengue, West Nile virus and the recently re-emerging Zika virus, are an increasing and probably lasting global risk. This Review summarizes and comments on the opportunities for broad-spectrum agents that are active against multiple flaviviruses. Broad-spectrum activity is particularly desirable to prepare for the next flaviviral epidemic, which could emerge from as-yet unknown or neglected viruses. Potential molecular targets for broad-spectrum antiflaviviral compounds include viral proteins, such as the viral protease or polymerase, and host targets that are exploited by these viruses during entry and replication, including α-glucosidase and proteins involved in nucleoside biosynthesis. Numerous compounds with broad-spectrum antiviral activity have already been identified by target-specific or phenotypic assays. For other compounds, broad-spectrum activity can be anticipated because of their mode of action and molecular targets.
黄病毒感染，如登革热、西尼罗河病毒和最近重新出现的寨卡病毒感染，是一个日益增加且可能持续存在的全球风险。本综述总结并评论了针对多种黄病毒具有活性的广谱药物的研发机会。鉴于下一次黄病毒疫情可能由未知或被忽视的病毒引发，广谱活性尤为重要。广谱抗黄病毒化合物的潜在分子靶点包括病毒蛋白，如病毒蛋白酶或聚合酶，以及这些病毒在进入和复制过程中利用的宿主靶点，包括α-葡萄糖苷酶和参与核苷生物合成的蛋白质。通过靶点特异性或表型分析已经鉴定出许多具有广谱抗病毒活性的化合物。对于其他化合物，由于其作用方式和分子靶点，也可预期具有广谱活性。
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