ORF1b

ORF1b is a large open reading frame at the 5' end of the genomes of coronaviruses and related nidoviruses. It overlaps the upstream ORF1a region and is translated as part of a frameshifting event that produces the pp1ab polyprotein in addition to the ORF1a-derived pp1a. Translation of ORF1b depends on a programmed -1 ribosomal frameshift, typically involving a slippery heptanucleotide sequence and a downstream RNA structure such as a pseudoknot; frameshifting efficiency varies among viruses and strains.

ORF1b encodes non-structural proteins nsps 12 through 16: nsp12 (RNA-dependent RNA polymerase, RdRp); nsp13 (helicase); nsp14 (exoribonuclease and N7-methyltransferase); nsp15 (endoribonuclease); and nsp16 (2'-O-methyltransferase). These nsps form the replication-transcription complex that conducts genome replication and transcription of subgenomic RNAs, which are required for viral gene expression.

After translation, pp1a and pp1ab are proteolytically cleaved by virus-encoded proteases, including papain-like protease (PLpro) and 3C-like protease (3CLpro), to yield mature nsps. The enzymatic activities of ORF1b-encoded proteins drive RNA synthesis, RNA processing, proofreading (notably by nsp14), and RNA capping, all essential for productive infection.

Significance: The ORF1b region is highly conserved among coronaviruses and represents a core component of the replication machinery. Its nsps are common targets for antiviral strategies, including inhibitors of RdRp activity, and are central to understanding coronavirus biology and pathogenesis.