The severe acute respiratory syndrome (SARS) is a contagious disease that killed hundreds and sickened thousands of people worldwide between November 2002 and July 2003. The nucleocapsid (N) protein of the coronavirus responsible for this disease plays a critical role in vital assembly and maturation and is of particular interest because of its potential as an antiviral target or vaccine candidate. Refolding of SARS N-protein during production and purification showed the presence of two additional protein hands by SDS-PAGE. Mass spectroscopy (MALDI, SELDI, and LC/MS) confirmed that the hands are proteolytic products of N-protein and the cleavage sites are four SR motifs in the serine-arginine-rich region-sites not Suggestive of any known protease. Furthermore, results Of Subsequent testing for contaminating protease(s) were negative: cleavage appears to be due to inherent instability and/or autolysis. The importance of N-protein proteolysis to vital life cycle and thus to possible treatment directions are discussed. (C) 2008 Elsevier Inc. All rights reserved.