To date, five human coronaviruses (CoV) have been identified including severe acute respiratory syndrome (SARS).The SARS epidemic of 2002/ 2003 spread to more than 30 countries and had fatality rate of nearly 10%. The SARS genome encodes a number of proteases including papain like protease (PLpro) . Initially, it was reported that SARS PLpro was a deubiquitylase, however subsequent work has shown that PLpro is preferentially a deISGylase. PLpro cleaves ISG15-PLA2 and Ub-PLA2 with high and low efficiency respectively.