West Nile virus drug discovery.
West Nile virus drug discovery.
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西尼罗河病毒发现。
DOI：
10.3390/v5122977
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发表时间：
2013-12-03
期刊：
影响因子：
--
通讯作者：
Shi PY
中科院分区：
文献类型：
--
作者：
Lim SP;Shi PY
1999年在美国爆发的西尼罗河病毒（WNV）及其在美洲、欧洲部分地区、中东和非洲的持续传播，强调了开发西尼罗河病毒抗病毒药物的必要性。在这里，我们回顾了西尼罗河病毒药物发现的现状。WNV抑制剂的筛选方法包括基于病毒感染的筛选、基于酶的筛选、基于结构的虚拟筛选、基于结构的原理设计和基于抗体的治疗。这些努力已经产生了对病毒复制至关重要的病毒或细胞因子的抑制剂。对于小分子抑制剂，尚未开发出有希望的临床前候选药物;由于其药物样性质较差，大多数抑制剂甚至无法进入靶向优化阶段。然而，为黄病毒科的相关成员开发的几种抑制剂，如登革热病毒和丙型肝炎病毒，表现出对WNV的交叉抑制，这表明有可能将这些抗病毒药物重新用于WNV治疗。最有希望的是，治疗性抗体在小鼠模型中显示出优异的功效;其中一种抗体已进入临床试验。在过去的十五年中积累的知识为正在进行的WNV和其他黄病毒抗病毒药物的开发提供了更好的理论基础。
The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development.
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