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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cheng, Yih-shyun E. Kuo, Chih-jung Liang, Po-huang Liu, Rai-shung Fang, Jim-min Ma, Shiou-hwa Juan, Hsueh-fen Wu, Chung-yi Wong, Chi-huey Hsu, Hsien-hua Brik, Ashraf Huang, Hsuan-cheng Chen, Shui-tein Liang, Fu-sen Wu, Douglass Jan, Jia-tsrong |
| Description | Author Affiliation: Wu CY ( Genomics Research Center and Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.); |
| Abstract | 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). |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 27 |
| Volume Number | 101 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2004-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antiviral Agents Pharmacology SARS Virus Drug Effects Animals Blotting, Western Cercopithecus Aethiops Cysteine Endopeptidases Endopeptidases Enzyme-Linked Immunosorbent Assay Flow Cytometry Fluorescent Antibody Technique Vero Cells Viral Proteins Antagonists & Inhibitors Virus Replication Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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