This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yi, L. Articles by Xu, X. Search for Related Content PubMed PubMed Citation Articles by Yi, L. Articles by Xu, X.

 Previous Article  |  Next Article 

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.

---

* 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.

---

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.

This article has been cited by other articles:

• Wong, S. S. Y., Yuen, K.-Y. (2008). The management of coronavirus infections with particular reference to SARS. J Antimicrob Chemother 62: 437-441 [Abstract] [Full Text]  
• Severson, W. E., Shindo, N., Sosa, M., Fletcher, T. III, White, E. L., Ananthan, S., Jonsson, C. B. (2007). Development and Validation of a High-Throughput Screen for Inhibitors of SARS CoV and Its Application in Screening of a 100,000-Compound Library. J Biomol Screen 12: 33-40 [Abstract]  
• Neuman, B. W., Stein, D. A., Kroeker, A. D., Churchill, M. J., Kim, A. M., Kuhn, P., Dawson, P., Moulton, H. M., Bestwick, R. K., Iversen, P. L., Buchmeier, M. J. (2005). Inhibition, Escape, and Attenuated Growth of Severe Acute Respiratory Syndrome Coronavirus Treated with Antisense Morpholino Oligomers. J. Virol. 79: 9665-9676 [Abstract] [Full Text]