ORF1ab

ORF1ab (also ORF1a/b) refers collectively to two open reading frames (ORFs), ORF1a and ORF1b, that are conserved in the genomes of nidoviruses, a group of viruses that includes coronaviruses.

The genes express large polyproteins that undergo proteolysis to form several nonstructural proteins with various functions in the viral life cycle, including proteases and the components of the replicase-transcriptase complex (RTC).

[3] They undergo auto-proteolysis to release the nonstructural proteins due to the actions of internal cysteine protease domains.

[3] This proofreading functionality is thought to be required for sufficient fidelity to replicate large RNA genomes, but may also play additional roles in some viruses.

[9] In coronaviruses, pp1a and pp1ab together contain sixteen nonstructural proteins, which have the following functions:[1][2][10][11] The structure and organization of the genome, including ORF1a, ORF1b, and the frameshift separating them, is conserved among nidoviruses.

[4][12] In these non-canonical genomes, other frameshift locations or stop codon readthrough may be used to regulate the stoichiometry of viral proteins.

[4] The larger nidovirus genomes (above around 20kb[3]) encode a proofreading exoribonuclease (nsp14 in coronaviruses) thought to be required for replication fidelity.

Top: Organization of the coronavirus genome, illustrating nonstructural proteins within ORF1a and ORF1b. Middle: Domain organization of nsp14 ( exonuclease and methyltransferase ). Bottom: Components of the coronavirus replicase-transcriptase complex . [ 8 ]
Phylogenetic relationships between nidoviruses and their pp1ab protein domain organization, with conserved domains highlighted. NendoU represents the endoribonuclease and 3CLpro represents the main 3C-like protease . [ 4 ]