Small molecules targeting severe acute respiratory syndrome human coronavirus

Chung Yi Wu, Jia Tsrong Jan, Shiou Hwa Ma, Chin Jung Kuo, Hsueh Fen Juan, Yih Shyun E. Cheng, Hsien Hua Hsu, Hsuan Cheng Huang, Douglass Wu, Ashraf Brik, Fu Sen Liang, Rai Shung Liu, Jim Min Fang, Shui Tein Chen, Po Huang Liang, Chi Huey Wong

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451 Scopus citations


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, ≈50 compounds were found active at 10 μM; 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 μM. The 50% inhibitory concentrations for the inhibition of viral replication (EC50) and host growth (CC 50) were then measured and the selectivity index (SI = CC 50/EC50) was determined. The EC50, based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 μM (SI = 7.3), 6.0 μM (SI = 2.5), and 0.85 μM (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 (Ki = 0.6 μM).

Original languageEnglish
Pages (from-to)10012-10017
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number27
StatePublished - 6 Jul 2004
Externally publishedYes

ASJC Scopus subject areas

  • General


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