ORF1ab

ORF1a is the first open reading frame at the 5' end of the genome. Together ORF1ab occupies about two thirds of the genome, with the remaining third at the 3' end encoding the structural proteins and accessory proteins. ORF1ab sequences have been observed in noncanonical subgenomic RNAs, though their functional significance is unclear. or 45-70% in SARS-CoV-2 yielding a stoichiometry of roughly 1.5 to 2 times as much pp1a as pp1ab protein expressed. ==Processing==

and methyltransferase). Bottom: Components of the coronavirus replicase-transcriptase complex. The polyproteins pp1a and pp1ab contain about 13 to 17 nonstructural proteins. They undergo auto-proteolysis to release the nonstructural proteins due to the actions of internal cysteine protease domains. In coronaviruses, there are a total of 16 nonstructural proteins; pp1a protein contains nonstructural proteins nsp1-11 and the pp1ab protein contains nsp1-10 and nsp12-16. Proteolytic processing is performed by two proteases: the papain-like protease protein domain located in the multidomain protein nsp3 cleaves up to nsp4, and the 3CL protease (also known as the main protease, nsp5) performs the remaining cleavages of nsp5 through the polyprotein C-terminus. Proteins nsp12-16, the C-terminal components of the pp1ab polyprotein, contain the core enzymatic activities necessary for viral replication. After proteolytic processing, several of the nonstructural proteins assemble into a large protein complex known as the replicase-transcriptase complex (RTC) which performs genome replication and transcription. ==Components==

Core replicase domains organization, with conserved domains highlighted. NendoU represents the endoribonuclease and 3CLpro represents the main 3C-like protease. (This is sometimes considered seven domains, counting the transmembrane regions separately. ==Evolution==

The structure and organization of the genome, including ORF1a, ORF1b, and the frameshift separating them, is conserved among nidoviruses. Some "non-canonical" nidovirus structures have been described, mainly involving gene fusions. In these non-canonical genomes, other frameshift locations or stop codon readthrough may be used to regulate the stoichiometry of viral proteins. Some PCR tests that detect COVID-19 analyze the specimen for the ORF1ab gene, among others. == References ==