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Journal of Virology, October 2004, p. 11334-11339, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11334-11339.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Small Molecules Blocking the Entry of Severe Acute Respiratory Syndrome Coronavirus into Host Cells

Ling Yi,^1, Zhengquan Li,^2, Kehu Yuan,^1, Xiuxia Qu,¹ Jian Chen,¹ Guangwen Wang,¹ Hong Zhang,¹ Hongpeng Luo,² Lili Zhu,² Pengfei Jiang,¹ Lirong Chen,² Yan Shen,¹ Min Luo,¹ Guoying Zuo,² Jianhe Hu,¹ Deliang Duan,² Yuchun Nie,¹ Xuanling Shi,¹ Wei Wang,¹ Yang Han,³ Taisheng Li,³ Yuqing Liu,⁴ Mingxiao Ding,¹ Hongkui Deng,^1* and Xiaojie Xu^2*

Department of Cell Biology and Genetics, College of Life Sciences,¹ College of Chemistry and Molecular Engineering, Peking University,² Department of Infectious Disease, PUMC Hospital, CAMS and PUMC, Beijing,³ Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, Peoples Republic of China⁴

Received 30 January 2004/ Accepted 14 June 2004

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS, which caused a global panic in 2003. We describe here the screening of Chinese herbal medicine-based, novel small molecules that bind avidly with the surface spike protein of SARS-CoV and thus can interfere with the entry of the virus to its host cells. We achieved this by using a two-step screening method consisting of frontal affinity chromatography-mass spectrometry coupled with a viral infection assay based on a human immunodeficiency virus (HIV)-luc/SARS pseudotyped virus. Two small molecules, tetra-O-galloyl-ß-D-glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV activity with a 50% effective concentration of 4.5 µM and a selective index of 240.0. The two-step screening method described here yielded several small molecules that can be used for developing new classes of anti-SARS-CoV drugs and is potentially useful for the high-throughput screening of drugs inhibiting the entry of HIV, hepatitis C virus, and other insidious viruses into their host cells.

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* Corresponding author. Mailing address for H. Deng: Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, Peoples Republic of China. Phone: 8610-6275-6474. Fax: 8610-6275-6474. E-mail: hongkui_deng{at}pku.edu.cn. Mailing address for X. Xu: College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, Peoples Republic of China. Phone: 8610-6275-7456. Fax: 8610-6275-1708. E-mail: xiaojxu{at}chem.pku.edu.cn.

L.Y., Z.L., and K.Y. contributed equally to this study.

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Journal of Virology, October 2004, p. 11334-11339, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11334-11339.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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