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.