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Small molecules targeting severe acute respiratory syndrome human coronavirus.


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).

SUBMITTER: Wu CY 

PROVIDER: S-EPMC454157 | biostudies-literature | 2004 Jul

REPOSITORIES: biostudies-literature

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Small molecules targeting severe acute respiratory syndrome human coronavirus.

Wu Chung-Yi CY   Jan Jia-Tsrong JT   Ma Shiou-Hwa SH   Kuo Chih-Jung CJ   Juan Hsueh-Fen HF   Cheng Yih-Shyun E YS   Hsu Hsien-Hua HH   Huang Hsuan-Cheng HC   Wu Douglass D   Brik Ashraf A   Liang Fu-Sen FS   Liu Rai-Shung RS   Fang Jim-Min JM   Chen Shui-Tein ST   Liang Po-Huang PH   Wong Chi-Huey CH  

Proceedings of the National Academy of Sciences of the United States of America 20040628 27


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  ...[more]

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