Severe acute respiratory syndrome coronavirus (SARS-CoV) proteins belong to it large group of proteins that is difficult to express in traditional expression systems. The ability to express and purify SARS-CoV proteins in large quantities is critical for basic research and for development of pharmaceutical agents. The work reported here demonstrates: (1) fusion of SUMO (small ubiquitin-related modifier), a 100 amino acid polypeptide, to the N-termini of SARS-CoV proteins dramatically enhances expression in Escherichia coli cells and (2) 6x His-tagged SUMO-fusions facilitate rapid purification of the viral proteins on it large scale. We have exploited the natural chaperoning properties of SUMO to develop an expression system suitable Cor proteins that cannot be expressed by traditional methodologies. A unique feature of the system is the SUMO tag, which enhances expression. facilitates purification, and can be efficiently cleaved by a SUMO-specific protease to generate native protein with a desired N-terminus. We have purified various SARS-CoV proteins under either native or denaturing conditions. These purified proteins have been used to generate highly specific polyclonal antibodies. Our study suggests that the SUMO-fusion technology will be useful for enhancing expression and purification of the viral proteins for structural and functional studies its well as Cor therapeutic uses, (c) 2005 Elsevier Inc. All rights reserved.