3.3.1.1 Papain-like proteinase (PLpro)
PLproteinase or nsp3 releases proteins is involved in both processes of coronavirus replication and infection of the host. Some studies have highlighted the importance of these protease inhibitors in other Coronaviruses. Ratia et al identified a compound, GRL0617, with an EC50 of 15 μM that inhibits SARS-CoV viral replication in Vero E6 cells (Ratia et al., 2008). PLpro inhibitors against MERS-CoV (Kilianski et al., 2013), HEV (Saraswat et al., 2020), etc have also been reported. Disulfiram, an approved drug to treat alcohol dependence, has been reported to inhibit the papain-like protease of MERS and SARS in cell cultures, but clinical approval of its effectiveness is lacking (Li and De Clercq, 2020). The inhibition of Pl pro can be considered as a promising target in the development of coronavirus drug discovery.