α-ketoamides have a ring coined the γ-lactam ring because it cleaves the peptide bond of the glutamate residue in the protease. These inhibitors with the γ-lactam ring have been shown to improve the protease inhibition properties by ten-fold. The side chains off of the P1’, P2, and P3 positions were changed for each the 11 inhibitors in this structural design based study. Additionally, this paper chose α-ketoamides as inhibitors because of the two hydrogen bonding acceptor locations, where other inhibitors, such as Michael acceptors and aldehydes, only have one. This allows for it to bind to the main protease better.