gms | German Medical Science

International Conference on SARS - one year after the (first) outbreak

08. - 11.05.2004, Lübeck

Structural genomics study of the SARS coronavirus - the crystal structures of SARS virus main protease (Mpro) and its complex with an inhibitor


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  • corresponding author presenting/speaker Zihe Rao - Laboratory of Structural Biology, Tsinghua University & National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

International Conference on SARS - one year after the (first) outbreak. Lübeck, 08.-11.05.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04sars11.02

The electronic version of this article is the complete one and can be found online at:

Published: May 26, 2004

© 2004 Rao.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



A newly identified coronavirus, SARS-CoV, is the etiological agent responsible for the outbreak of severe acute respiratory syndrome (SARS). SARS-CoV Mpro, which is a 34.6 kDa protease (also called the 3C-like Protease, 3CLpro), plays a pivotal role in mediating viral replication and transcription functions through extensive proteolytic processing two replicase polyproteins, pp1a (486 kDa) and pp1ab (790 kDa). Here we report the crystal structures of the SARS coronavirus main protease, Mpro, at different pH values and in complex with a specific inhibitor. The protease structure has a fold that can be described as an augmented serine-protease but with a Cys...His at the active site. This series of crystal structures, the first of any protein from the SARS virus, reveal substantial pH-dependent conformational changes, and an unexpected mode of inhibitor binding, providing a structural basis for rational drug design.


Yang H, Yang M, Ding Y, Liu Y, Lou Z, Zhou Z, Sun L, Mo L, Ye S, Pang H, Gao GF, Anand K, Bartlam M, Hilgenfeld R, Rao Z. (2003) The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proc. Natl. Acad. Sci. USA. 100(23):13190-5