Massé N, Selisko B, Malet H, Peyrane F, Debarnot C, Decroly E, Benarroch D, Egloff M-P, Guillemot J-C, Alvarez K, Canard B
CNRS et université d'Aix-Marseille I et II, UMR 6098, Architecture et fonction des macromolécules biologiques, AFMB-CNRS-ESIL, Case 925, 163 avenue de Luminy, 13288 Marseille Cedex 9.
Virologie (Montrouge). 2007 Apr 1;11(2):121-133. doi: 10.1684/vir.2011.8912.
This work reviews the opportunities and scientific bases in the development of anti-dengue drugs. The timeliness of anti-dengue drug development is addressed in the context of the growing impact of dengueworldwide and existing strategies to fight the virus. The antiviral approach in therapy or prophylaxis during an epidemic as well as the impact of recent technological advances in drug-discovery and antiviral chemotherapy on the development of anti-dengue drugs are discussed. An analysis of current sources of synthetic or natural drugs is provided. Finally, we summarize the current knowledge on dengue virus proteins, which are currently considered the most viable as drug targets, as the envelop protein E and non-structural proteins NS3 and NS5 carrying protease, helicase, RNA triphosphatase, methyltransferase and RNA-dependent RNA polymerase activities. Other viral proteins proposed to be part of the replication complex and the complex itself are considered as potential targets of anti-dengue drugs. State-of-the-art methods are listed, that are expected to allow the discovery, design, and characterisation of anti-dengue drugs effective against the four serotypes.
本文综述了抗登革热药物研发的机遇和科学依据。鉴于登革热在全球范围内的影响日益增大以及现有的抗病毒策略，探讨了抗登革热药物研发的及时性。讨论了在疫情期间治疗或预防的抗病毒方法，以及药物发现和抗病毒化疗方面的最新技术进展对抗登革热药物研发的影响。提供了对当前合成或天然药物来源的分析。最后，我们总结了目前关于登革热病毒蛋白的知识，这些蛋白目前被认为是最可行的药物靶点，如具有蛋白酶、解旋酶、RNA三磷酸酶、甲基转移酶和RNA依赖性RNA聚合酶活性的包膜蛋白E以及非结构蛋白NS3和NS5。其他被认为是复制复合体一部分的病毒蛋白以及复制复合体本身也被视为抗登革热药物的潜在靶点。列出了一些先进方法，有望用于发现、设计和表征对四种血清型均有效的抗登革热药物。
