The release of the viral genome of the novel Wuhan coronavirus prompted us to construct first-generation homology models of the new CoV 3CL pro . Initial studies and BLAST analysis indicated that the virus was most closely related to a clade of bat coronaviruses (Figure ), of which the closest neighbour for which there was protease structural information available in the Protein Data Bank (www.rcsb.org) was bat coronavirus HKU4. EMBOSS Needle 18 alignment of the Wuhan genome with the sequence extracted from PDB:2YNB identified a putative 306ss viral 3CL pro protein with 49% sequence identity (65% sequence similarity) (Figure ). An initial Swissmodel search for possible homology model templates against this search sequence however provided only SARS protease templates with much higher sequence identity and similarity (96, 99% respectively). This was confirmed via a second EMBOSS Needle alignment (Figure ), and visually by a mapping of differing residues onto the respective crystal structures (Figure ). Alignment of the SARS 2z9j and HKU4 2ynb protease crystal structures however showed that the two had a very similar overall fold with an RMSD of 0.66Å across 229 well conserved Ca atoms. Accordingly, due to their higher overall sequence identities, SARS crystal structures were chosen for the future development of Wuhan CoV protease homology models. Coronavirus crystal structures are predominantly homodimers, and as a consequence Swissmodel template searches returned some duplicates arising from both chains A&B being selected. Models were built as homodimers where appropriate however for visualisation and initial refinement purposes the monomers were used (Table , Figure ). Pairs 1&3, 4&5 were functionally identical so only 6 models were taken through for further refinement. The 5 Swissmodel dimer models 1,2,4,6,7 were refined as both dimers and monomers, using Schrodinger Suite 2019 and monomer model 8 was refined without reconstruction to a dimer. The models were overlaid as their monomers and compared by manual inspection. The models were very structurally similar, especially in the active site region near His41 and Cys145 (Figure ). These models were also analysed using 100ns molecular dynamics simulations (see Supporting Information) to check the systems for overall structural stability (Figure ). In general the dimeric forms were slightly more stable overall, as the C-and N-termini of the chains form part of the dimer interface and are held more closely than in the monomeric state where they are more mobile. Finally an analysis of the new Wuhan coronavirus genome revealed multiple sites, analogous to those found or proposed for SARS that may be cleaved by the 3CLpro after (L/F/M)-Gln residues. These are mostly identical to the SARS sequences (Table ).