Proteases are an important class of drug target, most successfully in the cases of HIV protease and Hepatitis C 8 . Recent human outbreaks of related coronaviruses SARS in 2002 and MERS in 2012 have focused the world's attention on the global risks of such emerging viruses. Coronaviruses are positive strand, enveloped RNA viruses with exceptionally large genomes which usually encode two or three viral proteases. In the case of Severe Acute Respiratory Syndrome coronavirus, the two proteases are a papain-like cysteine protease (PL pro ) and a chymotrypsin-like cysteine protease 3CL pro , also known as the Main protease. SARS-CoV 3CL pro is essential for viral replication and is thus recognized as a potential drug target for the treatment of SARS infections. To date there are no clinically used inhibitors of the SARS protease yet they remain in development. The active site of SARS-CoV 3CL pro is located in the cleft between domains I and II of the protein, and the two domains each contribute one residue to the catalytic dyad composed of His41 and Cys145 (Figure ). Substrates and inhibitors typically contain Gln residues at the P1 position and large hydrophobic residues Phe/Leu/Met at P2. The wealth of medicinal chemistry and biochemical information gained over the last 18 years, coupled with good-high sequence similarity between the members of the coronavirus family makes the homology modelling of new and emerging viruses an inviting prospect.