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. 2017 Jun 23;419:1–42. doi: 10.1007/82_2017_25

Fig. 1.

Fig. 1

Outline of the coronavirus replicative cycle and replicase polyprotein organization, based on SARS-CoV. a Schematic overview of the coronavirus replicative cycle. Following entry by receptor-mediated endocytosis and release of the genome into the cytosol, genome translation yields the pp1a and pp1ab replicase polyproteins. Following polyprotein cleavage by multiple internal proteases, the viral nsps assemble into an RTC that engages in minus-strand RNA synthesis. Both full-length and subgenome (sg)-length minus strands are produced, with the latter templating the synthesis of the sg mRNAs required to express the structural and accessory protein genes residing in the 3′-proximal quarter of the genome. Ultimately, novel genomes are packaged into nucleocapsids that become enveloped by budding from smooth intracellular membranes, after which the new virions leave the cell by following the exocytic pathway. See text for more details. b The 14 open reading frames in the genome are indicated, i.e., the replicase ORFs 1a and 1b, the four common CoV structural protein genes (S, E, M, and N) and the ORFs encoding so-called ‘accessory proteins.’ The bottom panel explains the organization and proteolytic processing of the pp1a and pp1ab replicase polyproteins, the latter being produced by −1 ribosomal frameshifting. The nsp3 (PLpro) and nsp5 (3CLpro) proteases and their cleavage sites are indicated in matching colors. The resulting 16 cleavage products [nonstructural proteins (nsps)] are indicated, as are the conserved replicase domains. Domain abbreviations and corresponding nsp numbers: PLpro, papain-like proteinase (nsp3); 3CLpro, 3C-like protease (nsp5); TM, transmembrane domain (nsp3, nsp4, and nsp6); NiRAN, nidovirus RdRp-associated nucleotidyl transferase (nsp12); RdRp, RNA-dependent RNA polymerase (nsp12); ZBD, zinc-binding domain (nsp13); HEL1, superfamily 1 helicase (nsp13); ExoN, exoribonuclease (nsp14); N7-MT, N7-methyl transferase (nsp14); endoU, uridylate-specific endoribonuclease (nsp15); 2′-O-MT, 2′-O-methyl transferase (nsp16). Adopted with permission from (Snijder et al. 2016)