Severe acute respiratory syndrome coronavirus papain-like protease (PLpro)

The severe acute respiratory syndrome coronavirus papain-like protease (PLpro) is a cysteine protease encoded by coronaviruses, including SARS-CoV and SARS-CoV-2[2][3]. It is responsible for cleaving the N-terminus of the viral replicase polyprotein, an essential step for viral replication[2][3]. In addition to proteolytic activity, PLpro removes ubiquitin and ISG15 from host cell proteins, disrupting host antiviral pathways and aiding immune evasion[3][4]. The enzyme adopts a fold similar to known deubiquitinating enzymes but has unique structural features, including an intact zinc-binding motif and a specialized ubiquitin-like N-terminal domain[2]. PLpro is considered a critical antiviral drug target; inhibitors such as GRL0617 derivatives block its activity and are being explored for therapeutic use[1][4][5]. Its dual roles in viral propagation and suppression of host immunity make it both a potent virulence factor and a key focus for antiviral development.

Other names

SARS-CoV papain-like proteasePLproSARS coronavirus papain-like proteaseSARS PLproPapain-like protease

Inhibition of viral polyprotein cleavage, blocking viral replication\nInhibition of deubiquitinating/delSGylating activity, potentially restoring host antiviral response