Inhibitors of SARS-CoV entry--identification using an internally-controlled dual envelope pseudovirion assay.
Inhibitors of SARS-CoV entry--identification using an internally-controlled dual envelope pseudovirion assay.
复制标题
SARS-COV进入的抑制剂 - 使用内部控制的双信封假旋转测定法。
DOI：
10.1016/j.antiviral.2011.07.016
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发表时间：
2011-11
影响因子：
7.6
通讯作者：
Simmons, Graham
中科院分区：
文献类型：
--
作者：
Zhou, Yanchen;Agudelo, Juliet;Lu, Kai;Goetz, David H.;Hansell, Elizabeth;Chen, Yen Ting;Roush, William R.;McKerrow, James;Craik, Charles S.;Amberg, Sean M.;Simmons, Graham
关键词：
我们描述了一种筛选病毒进入抑制剂的新方法。纳入内部控制信封控制特异性。该检测系统适用于大多数包膜病毒。实施了SARS-CoV进入抑制剂的筛选实例。许多化合物被鉴定为抑制SARS-CoV进入和复制。严重急性呼吸综合征相关冠状病毒（SARS-CoV）是一种地方性非典型肺炎的病原体，感染了全世界数千人。虽然已经描述了许多有希望的潜在SARS-CoV疫苗和治疗剂，但目前没有有效的抗SARS-CoV的抗病毒药物。病毒进入过程的复杂性和连续性为药物开发提供了多个有效靶点。在这里，我们描述了一种快速，安全的基于细胞的高通量筛选系统，双包膜假病毒体（DEP）检测，特异性筛选抑制剂的病毒进入。该检测系统采用了一种新的双包膜策略，使用慢病毒假病毒颗粒作为靶点，其进入由SARS-CoV刺突糖蛋白驱动。第二个不相关的病毒包膜被用作内部对照，以减少假阳性的数量。作为该测定的功效的一个例子，报道了一类抑制剂，其在复制周期的两个步骤（病毒进入和颗粒组装）具有抑制SARS-CoV的潜力。该检测系统可以很容易地适用于筛选针对其他病毒的进入抑制剂，并仔细选择匹配的伴侣病毒包膜。
► We describe a novel assay for screening inhibitors of viral entry. ► The inclusion of an internal control envelope controls for specificity. ► This assay system can be adapted for most enveloped viruses. ► Examples of screens for inhibitors of SARS-CoV entry were performed. ► A number of compounds were identified that inhibit SARS-CoV entry and replication. Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, dual envelope pseudovirion (DEP) assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes.
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DOI：
10.1074/jbc.m508381200
发表时间：
2006-02-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huang IC;Bosch BJ;Li F;Li W;Lee KH;Ghiran S;Vasilieva N;Dermody TS;Harrison SC;Dormitzer PR;Farzan M;Rottier PJ;Choe H
通讯作者：
Choe H
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
3.7
作者：
Pager, CT;Craft, WW;Dutch, RE
通讯作者：
Dutch, RE
影响因子：
3.7
作者：
Kam YW;Okumura Y;Kido H;Ng LF;Bruzzone R;Altmeyer R
通讯作者：
Altmeyer R
影响因子：
5.4
作者：
GILBERT, JM;BATES, P;WHITE, JM
通讯作者：
WHITE, JM