The Martin lab, in collaboration with the Butts lab, has modeled and characterized 78 clinically relevant variants of the SARS-CoV-2 main protease (Mpro), representing all known mutations as of April 29, 2020. The team has been producing molecular models of each variant since the beginning of the pandemic. Mpro plays an important role in the replication process by cleaving large polyproteins into functional viral proteins. Modeling all sequence variants enables characterization of the mutational landscape available to this protein and offers insight into how mutations affect the active site cohesion of this cysteine protease. So far, substitutions tend toward larger and hydrophobic residues, and the active sites of the variant proteins tend to be less cohesive in the active dimer forms relative to the reference sequence. Future work will focus on designing mutation-resistant inhibitors.