SARS-CoV-1 papain-like protease (PLpro)

The SARS-CoV-1 papain-like protease (PLpro) is a critical enzyme encoded within the non-structural protein 3 (nsp3) of the SARS-CoV-1 genome (UniProt: P0C6X7). Its primary biological function is the proteolytic processing of the viral polyprotein 1a (pp1a) at the nsp1/2, nsp2/3, and nsp3/4 junctions, which is essential for the assembly of the viral replicase-transcriptase complex (PubMed: 18801847). Additionally, PLpro acts as a deubiquitinating and de-ISGylating enzyme, removing ubiquitin and ISG15 from host cell proteins to suppress the innate immune response, particularly the Type I interferon pathway (PubMed: 17350187). In the context of disease, PLpro is a major virulence factor that facilitates both viral replication and immune evasion during SARS infection. Therapeutic targeting of PLpro aims to inhibit its catalytic activity, thereby halting viral maturation and restoring the host's ability to mount an antiviral response. While several experimental inhibitors like GRL0617 have been identified, challenges remain regarding selectivity over human deubiquitinases (PubMed: 24524404).

Other names

Papain-like proteasePLPnsp3 papain-like proteaseSARS-CoV PLproNon-structural protein 3 papain-like protease

Inhibition of the cysteine protease activity of PLpro, which prevents the cleavage of the viral polyprotein 1a and blocks the deubiquitination and de-ISGylation of host proteins, thereby inhibiting viral replication and enhancing the host's innate immune response.