Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro
文献类型：期刊论文
| 作者 | Chen, LL; Gui, CS; Luo, XM ; Yang, QG; Gunther, S; Scandella, E; Drosten, C; Bai, D; He, XC; Ludewig, B
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| 刊名 | JOURNAL OF VIROLOGY
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| 出版日期 | 2005-06 |
| 卷号 | 79期号:11页码:7095-7103 |
| ISSN号 | 0022-538X |
| DOI | 10.1128/JVI.79.11.7095-7103.2005 |
| 文献子类 | Article |
| 英文摘要 | The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for anti-SARS-CoV drugs due to its crucial role in the viral life cycle. In this study, a database containing structural information of more than 8,000 existing drugs was virtually screened by a docking approach to identify potential binding molecules of SARS-CoV 3CL(pro). As a target for screening, both a homology model and the crystallographic structure of the binding pocket of the enzyme were used. Cinanserin (SQ 10,643), a well-characterized serotonin antagonist that has undergone preliminary clinical testing in humans in the 1960s, showed a high score in the screening and was chosen for further experimental evaluation. Binding of both cinanserin and its hydrochloride to bacterially expressed 3CL(pro) of SARS-CoV and the related human coronavirus 229E (HCoV-229E) was demonstrated by surface plasmon resonance technology. The catalytic activity of both enzymes was inhibited with 50% inhibitory concentration (IC50) values of 5 μ M, as tested with a fluorogenic substrate. The antiviral activity of cinanserin was further evaluated in tissue culture assays, namely, a replicon system based on HCoV-229E and quantitative test assays with infectious SARS-CoV and HCoV-229E. All assays revealed a strong inhibition of coronavirus replication at nontoxic drug concentrations. The level of virus RNA and infectious particles was reduced by up to 4 log units, with IC50 values ranging from 19 to 34 μ M. These findings demonstrate that the old drug cinanserin is an inhibitor of SARS-CoV replication, acting most likely via inhibition of the 3CL proteinase. |
| WOS关键词 | SARS-ASSOCIATED CORONAVIRUS ; SQ 10643 ; ORBITAL ELECTRONEGATIVITY ; MOLECULAR DOCKING ; GENOME SEQUENCE ; MAIN PROTEINASE ; NUCLEIC-ACIDS ; HONG-KONG ; ANTISEROTONIN ; PROTEASE |
| WOS研究方向 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000229085400054 |
| 出版者 | AMER SOC MICROBIOLOGY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273866]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Gunther, S |
| 作者单位 | 1.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 2.Bernhard Nocht Inst Trop Med, Dept Virol, D-20359 Hamburg, Germany 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med,Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Kanton Hosp, Dept Res, CH-9007 St Gallen, Switzerland |
| 推荐引用方式 GB/T 7714 | Chen, LL,Gui, CS,Luo, XM,et al. Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro[J]. JOURNAL OF VIROLOGY,2005,79(11):7095-7103. |
| APA | Chen, LL.,Gui, CS.,Luo, XM.,Yang, QG.,Gunther, S.,...&Jiang, HL.(2005).Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro.JOURNAL OF VIROLOGY,79(11),7095-7103. |
| MLA | Chen, LL,et al."Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro".JOURNAL OF VIROLOGY 79.11(2005):7095-7103. |
入库方式： OAI收割
来源：上海药物研究所
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