Nucleoside analogs as a rich source of antiviral agents active against arthropod-borne flaviviruses.
Nucleoside analogs as a rich source of antiviral agents active against arthropod-borne flaviviruses.
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DOI：
10.1177/2040206618761299
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发表时间：
2018-01
影响因子：
--
通讯作者：
Růžek D
中科院分区：
文献类型：
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作者：
Eyer L;Nencka R;de Clercq E;Seley-Radtke K;Růžek D
核苷类似物代表最大类别的基于小分子的抗病毒药物，其目前形成由HIV、B或丙型肝炎病毒和疱疹病毒引起的慢性感染的化疗的支柱。高抗病毒效力和有利的药代动力学参数使得一些核苷类似物也适用于治疗由其他医学上重要的RNA和DNA病毒引起的急性感染。本文综述了核苷类似物对黄病毒科黄病毒属节肢动物传播成员的抗病毒研究，主要集中在黄病毒RNA依赖的RNA聚合酶，甲基转移酶和解旋酶/NTR的核苷抑制剂的描述。细胞内核苷合成的抑制剂和新发现的具有高抗黄病毒效力的核苷衍生物引起了人们的注意，其作用方式目前还不完全清楚。此外，这篇综述强调了核苷类似物开发中的重要挑战和并发症，并提出了克服这些限制的可能策略。
Nucleoside analogs represent the largest class of small molecule-based antivirals, which currently form the backbone of chemotherapy of chronic infections caused by HIV, hepatitis B or C viruses, and herpes viruses. High antiviral potency and favorable pharmacokinetics parameters make some nucleoside analogs suitable also for the treatment of acute infections caused by other medically important RNA and DNA viruses. This review summarizes available information on antiviral research of nucleoside analogs against arthropod-borne members of the genus Flavivirus within the family Flaviviridae, being primarily focused on description of nucleoside inhibitors of flaviviral RNA-dependent RNA polymerase, methyltransferase, and helicase/NTPase. Inhibitors of intracellular nucleoside synthesis and newly discovered nucleoside derivatives with high antiflavivirus potency, whose modes of action are currently not completely understood, have drawn attention. Moreover, this review highlights important challenges and complications in nucleoside analog development and suggests possible strategies to overcome these limitations.