Chemical genetics identifies SARS inhibitors

Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV) recently emerged as the causative agent of an atypical pneumonia. Within a year the virus infected more than 8000 people in 29 countries and claimed more that 900 human lives. Lack of knowledge about the novel virus and the absence of therapeutics were the primary reasons that the outbreak could not be contained and managed efficiently. With the goal of finding effective drug leads with which to combat SARS, researchers from the University of Hong Kong conducted a chemical genetic screen to isolate compounds with anti-SARS-CoV activity. The group screened an initial library of 50,240 compounds and found that 104 were potent inhibitors of the virus; of these, two targeted the virus protease specifically, seven targeted the helicase, and 18 targeted a protein required for virus entry into cells. The successful identification of novel small-molecule anti-viral inhibitors validates chemical genetics as a rapid and effective approach with which to tackle emerging and existing diseases. Crucially, this study has provided a reservoir of novel biologically active small molecules that could be developed as anti-SARS therapeutics.

Richard Y. Kao, Wayne H.W. Tsui, Terri S.W. Lee, Julian A. Tanner, Rory M. Watt, Jian-Dong Huang, Lihong Hu, Guanhua Chen, Zhiwei Chen, Linqi Zhang, Tian He, Kwok-Hung Chan, Herman Tse, Amanda P.C. To, Louisa W.Y. Ng, Bonnie C.W. Wong, Hoi-Wah Tsoi, Dan Yang, David D. Ho, and Kwok-Yung Yuen: "Identification of Novel Small-Molecule Inhibitors of Severe Acute Respiratory Syndrome-Associated Coronavirus by Chemical Genetics"

Publishing in Chemistry & Biology, Volume 11, Number 9, September 2004, pages 1293–1299. DOI 10.1016/j.chembiol .2004.07.013

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