Fig 4. Visualization and summary of the L pro mutants used in this study. (A) Standard cartoon view of L pro (grey) bound to ISG15 (blue) (PDB: 6FFA). L pro L92 and L102 interact with ISG15 W123, this positions ISG15’s C-terminus (R153, L154 and G155) in the substrate binding cleft of L pro . � In this structure a C-terminal propargyl warhead replaced G155 [40]. Residues which upon mutation were reported to affect L pro ’s structure or function are shown as colored sticks. Green: C51A inactivates L pro ’s catalytic activity; red: I83A or L86A reduce the DUB activity and IFN induction; pink: L92A and L102A reduce affinity for ISG15; orange: C133S reduces affinity for eIF4G; aquamarine: L143A predicted to open substrate binding pocket. Drawings were generated using PyMOL. (B) Overview of the reported effects of the introduced mutations in L pro on the various proteolytic activities of L pro , this includes references and the category of the underlying experimental