High-throughput assay using a gfp-expressing replicon for sars-cov drug discovery
文献类型：期刊论文
| 作者 | Ge, Feng1; Xiong, Sheng1; Lin, Fu-Sen2; Zhang, Zhi-Ping3; Zhang, Xian-En3 |
| 刊名 | Antiviral research
 |
| 出版日期 | 2008-11-01 |
| 卷号 | 80期号:2页码:107-113 |
| 关键词 | Sars-cov replicon High-throughput screen (hts) |
| ISSN号 | 0166-3542 |
| DOI | 10.1016/j.antiviral.2008.05.005 |
| 通讯作者 | Ge, feng(tgfeng@jnu.edu.cn) |
| 英文摘要 | The causative agent of severe acute respiratory syndrome (sars) has been identified as a novel coronavirus, sars-cov. the development of rapid screening assays is essential for antiviral drug discovery. by using a cell line expressing a sars-cov subgenomic replicon, we developed a high-throughput assay and used it to screen small molecule compounds for inhibitors of sars-cov replication in the absence of live virus. the assay system involves minimal manipulation after assay set-up, facilitates automated read-out and minimizes risks associated with hazardous viruses. based on this assay system, we screened 7035 small molecule compounds from which we identified 7 compounds with anti-sars-cov activity. we demonstrate that the compounds inhibited sars-cov replication-dependent gfp expression in the replicon cells and reduced sars-cov viral protein accumulation and viral rna copy number in the replicon cells. in a sars-cov plaque reduction assay, these compounds were confirmed to have antiviral activity. the target of one of the hit compounds, c12344, was validated by the generation of resistant replicon cells and the identification of the mutations conferring the resistant phenotype. these compounds should be valuable for developing anti-sars therapeutic drugs as well as research tools to study the mechanism of sars-cov replication. (c) 2008 elsevier b.v. all rights reserved. |
| WOS关键词 | ACUTE RESPIRATORY SYNDROME ; SMALL-MOLECULE INHIBITORS ; SYNDROME-ASSOCIATED CORONAVIRUS ; MAIN PROTEASE ; IDENTIFICATION ; RNA ; GENETICS ; DESIGN |
| WOS研究方向 | Pharmacology & Pharmacy ; Virology |
| WOS类目 | Pharmacology & Pharmacy ; Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000260818300004 |
| 出版者 | ELSEVIER SCIENCE BV |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2375482 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Ge, Feng |
| 作者单位 | 1.Jinan Univ, Inst Life & Hlth Engn, Guangzhou 510632, Guangdong, Peoples R China 2.Singapore Gen Hosp, Div Res, Singapore Hlth Res Facil, Singapore 169611, Singapore 3.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ge, Feng,Xiong, Sheng,Lin, Fu-Sen,et al. High-throughput assay using a gfp-expressing replicon for sars-cov drug discovery[J]. Antiviral research,2008,80(2):107-113. |
| APA | Ge, Feng,Xiong, Sheng,Lin, Fu-Sen,Zhang, Zhi-Ping,&Zhang, Xian-En.(2008).High-throughput assay using a gfp-expressing replicon for sars-cov drug discovery.Antiviral research,80(2),107-113. |
| MLA | Ge, Feng,et al."High-throughput assay using a gfp-expressing replicon for sars-cov drug discovery".Antiviral research 80.2(2008):107-113. |
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来源：武汉病毒研究所
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