TY - JOUR
T1 - Small molecules targeting severe acute respiratory syndrome human coronavirus
AU - Wu, Chung Yi
AU - Jan, Jia Tsrong
AU - Ma, Shiou Hwa
AU - Kuo, Chin Jung
AU - Juan, Hsueh Fen
AU - Cheng, Yih Shyun E.
AU - Hsu, Hsien Hua
AU - Huang, Hsuan Cheng
AU - Wu, Douglass
AU - Brik, Ashraf
AU - Liang, Fu Sen
AU - Liu, Rai Shung
AU - Fang, Jim Min
AU - Chen, Shui Tein
AU - Liang, Po Huang
AU - Wong, Chi Huey
PY - 2004/7/6
Y1 - 2004/7/6
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=3142594446&partnerID=8YFLogxK
U2 - 10.1073/pnas.0403596101
DO - 10.1073/pnas.0403596101
M3 - Article
AN - SCOPUS:3142594446
SN - 0027-8424
VL - 101
SP - 10012
EP - 10017
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 27
ER -