SARS-CoV-2 3-chymotrypsin-like protease, papain-like protease, and helicase (3CLpro, PLpro, and nsp13)

The target complex described refers to three critical enzymes of the SARS-CoV-2 virus: the 3-chymotrypsin-like protease (3CLpro or Mpro), the papain-like protease (PLpro), and the helicase (nsp13). 3CLpro (nsp5) and PLpro (a domain of nsp3) are essential for the proteolytic processing of the viral polyproteins pp1a and pp1ab into functional non-structural proteins required for the viral replication-transcription complex (UniProt P0DTD1; PubMed: 32404437). PLpro additionally facilitates immune evasion by cleaving ubiquitin and ISG15 from host proteins, thereby antagonizing the innate immune response (PubMed: 32726803). The helicase (nsp13) is a highly conserved enzyme that unwinds double-stranded RNA in an ATP-dependent manner, a process vital for viral genome replication (PubMed: 32807195). Quercetin, a natural flavonoid, has been identified through in silico and in vitro studies as a potential multi-target inhibitor capable of binding to the active sites of these enzymes, particularly 3CLpro, to disrupt viral activity (PubMed: 33034336). This entry is marked as incorrect because it combines three distinct viral targets and a specific ligand (quercetin) into a single target designation.

Other names

Main proteaseMpronsp5Papain-like proteasensp3nsp13Non-structural protein 5Non-structural protein 3Non-structural protein 13SARS-CoV-2 3CLproSARS-CoV-2 PLproSARS-CoV-2 helicase

Quercetin acts as a multi-target inhibitor that binds to the active sites or allosteric pockets of 3CLpro, PLpro, and the helicase (nsp13), thereby inhibiting viral polyprotein processing and RNA replication.