Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells
Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells
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DOI：
10.1128/jvi.78.20.11334-11339.2004
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Xu, XJ
中科院分区：
文献类型：
--
作者：
Yi, L;Li, ZQ;Xu, XJ
严重急性呼吸综合征冠状病毒（SARS-CoV）是2003年引起全球恐慌的SARS的病原体。我们在这里描述的筛选中草药为基础的，新颖的小分子结合的SARS-CoV的表面刺突蛋白，从而可以干扰病毒进入其宿主细胞。我们实现了这一点，通过使用两步筛选方法组成的正面亲和色谱-质谱结合基于人类免疫缺陷病毒（HIV）-luc/SARS假型病毒的病毒感染检测。通过野生型SARS-CoV感染系统，证实了两个小分子TGG和木犀草素的抗SARS-CoV活性。TGG具有显著的抗SARS-CoV活性，50%有效浓度为4.5 μ M，选择指数为240.0。本文描述的两步筛选方法产生了几种小分子，可用于开发新的抗SARS冠状病毒药物，并可能用于高通量筛选抑制HIV，丙型肝炎病毒和其他潜伏病毒进入其宿主细胞的药物。
Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS, which caused a global panic in 2003. We describe here the screening of Chinese herbal medicine-based, novel small molecules that bind avidly with the surface spike protein of SARS-CoV and thus can interfere with the entry of the virus to its host cells. We achieved this by using a two-step screening method consisting of frontal affinity chromatography-mass spectrometry coupled with a viral infection assay based on a human immunodeficiency virus (HIV)-luc/SARS pseudotyped virus. Two small molecules, tetra-O-galloyl-beta-D-glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV activity with a 50% effective concentration of 4.5 muM and a selective index of 240.0. The two-step screening method described here yielded several small molecules that can be used for developing new classes of anti-SARS-CoV drugs and is potentially useful for the high-throughput screening of drugs inhibiting the entry of HIV, hepatitis C virus, and other insidious viruses into their host cells.