Severe acute respiratory syndrome coronavirus 2 open reading frame 1ab messenger RNA (SARS-CoV-2 ORF1ab mRNA)

SARS-CoV-2 ORF1ab mRNA is the primary transcript and genomic component of the Severe Acute Respiratory Syndrome Coronavirus 2, covering approximately 20,000 nucleotides of the 5' end of the viral genome [7, 13]. It encodes the large polyproteins pp1a and pp1ab, which are processed into 16 non-structural proteins (nsps) that form the replication-transcription complex (RTC) [1, 5, 13]. This complex is responsible for all aspects of viral RNA synthesis, including the replication of the genomic RNA and the transcription of subgenomic mRNAs [6, 15]. The translation of ORF1ab involves a highly conserved programmed -1 ribosomal frameshift element, which is essential for the production of the pp1ab polyprotein containing the RNA-dependent RNA polymerase (RdRp) [7, 13]. Due to its indispensable role in the viral life cycle and its high degree of conservation among variants, ORF1ab mRNA is a major therapeutic target for RNA-based interventions such as antisense oligonucleotides (ASOs) and siRNAs [2, 4, 11]. These therapies aim to inhibit viral replication by inducing RNA degradation or blocking the translation of essential replication proteins [4, 12].

Other names

ORF1ab geneReplicase geneSARS-CoV-2 genomic RNApp1ab mRNASARS-CoV-2 ORF1ab transcript

Drugs targeting SARS-CoV-2 ORF1ab mRNA typically function through RNase H-mediated degradation of the viral RNA, steric hindrance of the translation machinery, or disruption of the programmed -1 ribosomal frameshifting element required for pp1ab synthesis [2, 4, 12].