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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Small molecules targeting severe acute respiratory syndrome human coronavirus.
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Small molecules targeting severe acute respiratory syndrome human coronavirus.

机译：针对严重急性呼吸综合征人类冠状病毒的小分子。

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摘要

Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel human coronavirus. Currently, no effective antiviral agents exist against this type of virus. A cell-based assay, with SARS virus and Vero E6 cells, was developed to screen existing drugs, natural products, and synthetic compounds to identify effective anti-SARS agents. Of >10,000 agents tested, approximately 50 compounds were found active at 10 microM; among these compounds, two are existing drugs (Reserpine 13 and Aescin 5) and several are in clinical development. These 50 active compounds were tested again, and compounds 2-6, 10, and 13 showed active at 3 microM. The 50% inhibitory concentrations for the inhibition of viral replication (EC(50)) and host growth (CC(50)) were then measured and the selectivity index (SI = CC(50)/EC(50)) was determined. The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 microM (SI = 7.3), 6.0 microM (SI = 2.5), and 0.85 microM (SI = 80), respectively. Additional studies were carried out to further understand the mode of action of some active compounds, including ELISA, Western blot analysis, immunofluorescence and flow cytometry assays, and inhibition against the 3CL protease and viral entry. Of particular interest are the two anti-HIV agents, one as an entry blocker and the other as a 3CL protease inhibitor (K(i) = 0.6 microM).
机译：严重急性呼吸系统综合症（SARS）是一种由新型人类冠状病毒引起的传染病。当前，不存在针对这种病毒的有效抗病毒剂。已开发出一种基于细胞的检测SARS病毒和Vero E6细胞的方法，以筛选现有药物，天然产物和合成化合物，以鉴定有效的抗SARS药物。在测试的10,000多种试剂中，发现约有50种化合物的活性为10 microM；在这些化合物中，有两种是现有药物（利血平13和七叶皂苷5），有几种正在临床开发中。再次测试了这50种活性化合物，化合物2-6、10和13在3 microM下显示出活性。然后测量抑制病毒复制（EC（50））和宿主生长（CC（50））的50％抑制浓度，并确定选择性指数（SI = CC（50）/ EC（50））。基于ELISA的EC（50）和利血平，Aescim和Valinomycin的SI分别为3.4 microM（SI = 7.3），6.0 microM（SI = 2.5）和0.85 microM（SI = 80）。为了进一步了解某些活性化合物的作用方式，还进行了其他研究，包括ELISA，Western印迹分析，免疫荧光和流式细胞术测定以及对3CL蛋白酶和病毒进入的抑制作用。特别令人感兴趣的是两种抗HIV药物，一种是进入阻断剂，另一种是3CL蛋白酶抑制剂（K（i）= 0.6 microM）。

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