Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells.

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

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-beta-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 microM 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.