The role of cysteine peptidases in coronavirus cell entry and replication: The therapeutic potential of cathepsin inhibitors
Fig 1
Schematic representation of the SARS-CoV and SARS-CoV-2 genome (A) and the replicase polyproteins (B). The genomic RNA comprises 2 parts, of which the first part (ORF1a and ORF1b) directly translates into 2 polyproteins pp1a and pp1ab due to a −1 frameshift between the 2 ORFs (orange arrow). They are composed of 16 Nsps (Nsp1–Nsp16) that form the replication–transcription complex. The polyproteins are processed into mature Nsps by the 2 peptidases as indicated in panel B by black and white triangles, namely Mpro, which is Nsp5, cleaves the polyprotein at 11 sites and PLpro, which is part of the Nsp3, performs cleavage at 3 sites. Among the released Nsps are RdRp (Nsp12) and RNA helicase (Nsp13). The 3′ third of the genome encodes the structural and accessory proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) shown in green and gray. Nsp, nonstructural protein; ORF, open reading frame; RdRp, RNA-dependent RNA polymerase; SARS-CoV, Severe Acute Respiratory Syndrome Coronavirus; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2.