Coronavirus proteases, such as SARS-CoV-2, papain-like protease (PLpro for papain-like protease) and 3C-like protease (3CLpro for 3C-like protease), are attractive antiviral targets because they are essential for coronavirus replication. PLPro is a protease located in the non-structural protein 3 (NS3) of the viral polypeptide. PLpro has the additional function of removing ubiquitin and ISG15 from host cell proteins to help coronaviruses evade the host's innate immune responses. Indeed, the action of PLpro disrupts the signalling pathways of INF beta and NF-kappa B. Targeting papain-like protease with antiviral drugs may have an advantage not only by inhibiting viral replication, but also by inhibiting the disruption of signaling cascades in infected cells that can lead to cell death in surrounding uninfected cells.