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Journal of Virology, September 2008, p. 8647-8655, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00298-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Structure of the Main Protease from a Global Infectious Human Coronavirus, HCoV-HKU1{triangledown} ,{dagger}

Qi Zhao,1 Shuang Li,1 Fei Xue,1 Yilong Zou,1 Cheng Chen,1 Mark Bartlam,2 and Zihe Rao1,2,3*

Tsinghua-Nankai-IBP Joint Research Group for Structural Biology, Tsinghua University, Beijing 100084, China,1 College of Life Sciences and Tianjin State Laboratory of Protein Sciences, Nankai University, Tianjin 300071, China,2 National Laboratory of Biomacromolecules, Institute of Biophysics (IBP), Chinese Academy of Sciences, Beijing 100101, China3

Received 11 February 2008/ Accepted 10 June 2008

The newly emergent human coronavirus HKU1 (HCoV-HKU1) was first identified in Hong Kong in 2005. Infection by HCoV-HKU1 occurs worldwide and causes syndromes such as the common cold, bronchitis, and pneumonia. The CoV main protease (Mpro), which is a key enzyme in viral replication via the proteolytic processing of the replicase polyproteins, has been recognized as an attractive target for rational drug design. In this study, we report the structure of HCoV-HKU1 Mpro in complex with a Michael acceptor, inhibitor N3. The structure of HCoV-HKU1 provides a high-quality model for group 2A CoVs, which are distinct from group 2B CoVs such as severe acute respiratory syndrome CoV. The structure, together with activity assays, supports the relative conservation at the P1 position that was discovered by sequencing the HCoV-HKU1 genome. Combined with structural data from other CoV Mpros, the HCoV-HKU1 Mpro structure reported here provides insights into both substrate preference and the design of antivirals targeting CoVs.

* Corresponding author. Mailing address: Laboratory of Structural Biology, Life Sciences Building, Tsinghua University, Beijing 100084, China. Phone: 86 10 62771493. Fax: 86 10 62773145. E-mail: raozh{at}xtal.tsinghua.edu.cn

{triangledown} Published ahead of print on 18 June 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, September 2008, p. 8647-8655, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00298-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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