基于高通量筛选的新型西尼罗河病毒抑制剂的发现。
HTS-driven discovery of new chemotypes with West Nile Virus inhibitory activity.
机构信息
Department of Biochemistry and Molecular Biology, Southern Research Institute, 2000 9th Ave S. Birmingham, AL 35205, USA.
出版信息
Molecules. 2010 Mar 12;15(3):1690-704. doi: 10.3390/molecules15031690.
West Nile virus (WNV) is a positive sense, single-stranded RNA virus that can cause illness in humans when transmitted via mosquito vectors. Unfortunately, no antivirals or vaccines are currently available, and therefore efficient and safe antivirals are urgently needed. We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells. A primary screen of a 13,001 compound library at a 10 microM final concentration was conducted using the 384-well format. Z' values ranged from 0.54-0.83 with a median of 0.74. Average S/B was 17 and S/N for each plate ranged from 10.8 to 23.9. Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay. Seven compounds showed potential as small molecule probes directed at WNV. The hit rate from the primary screen was 0.185% (24 compounds out of 13,001 compounds) and from the secondary screens was 0.053% (7 out of 13,001 compounds) respectively.
西尼罗河病毒（WNV）是一种正链单链 RNA 病毒，当通过蚊子媒介传播时会导致人类患病。不幸的是，目前没有抗病毒药物或疫苗，因此迫切需要高效和安全的抗病毒药物。我们开发了一种高通量筛选方法，以发现抑制 Vero E6 细胞病毒感染的小分子探针。使用 384 孔格式对终浓度为 10 μM 的 13001 种化合物文库进行了初步筛选。Z' 值范围为 0.54-0.83，中位数为 0.74。平均 S/B 为 17，每个平板的 S/N 范围为 10.8 至 23.9。26 种化合物在 HT 筛选中表现出剂量反应，并在添加时间测定和滴度降低测定中进一步评估。七种化合物显示出作为针对 WNV 的小分子探针的潜力。初级筛选的命中率为 0.185%（24 种化合物中有 13001 种化合物），次级筛选的命中率为 0.053%（7 种化合物中有 13001 种化合物）。
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