Fig. 3. Structure of SARS-CoV-2 ^Mpro and inhibitors in its active site. The unique dimer structure of ^Mpro (left) offers one distinct path to block its catalytic activity through the substrate-binding pocket. The active site can be partitioned into subpockets (right) to rationalize the design strategy against SARS-CoV-2 ^Mpro. The four main pockets P4, P2, P1, and P1′ (colored blue, teal, orange, and green, respectively) need to be occupied for optimal inhibition of ^Mpro. Ligands are represented in colored sticks in the active site. PF-00835231: grey; GC376: orange; 11b: green; N3: purple; 13: red.