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

The SARS-CoV-2 ORF1ab gene is the largest open reading frame in the viral genome, occupying approximately two-thirds of the total RNA sequence. It encodes two massive polyproteins, pp1a and pp1ab, which are post-translationally cleaved by viral proteases into 16 non-structural proteins (nsps) essential for the viral life cycle (UniProt: P0DTD1). These nsps form the replicase-transcriptase complex, which includes the RNA-dependent RNA polymerase (RdRp), helicase, and proteases like the main protease (Mpro) and papain-like protease (PLpro) (PubMed: 32275855). Because it encodes the core machinery for viral replication, ORF1ab is the primary target for diagnostic RT-PCR assays and a major focus for antiviral drug development. Therapeutic strategies include small molecules that inhibit the encoded enzymes, such as Remdesivir and Nirmatrelvir, as well as experimental RNA-interference (RNAi) technologies designed to target the ORF1ab RNA sequence itself to prevent protein synthesis (PubMed: 33053324).

Other names

ORF1abReplicase polyprotein 1abpp1abSARS-CoV-2 replicase geneSARS-CoV-2 RNA-dependent RNA polymerase gene

Inhibition of viral replication through RNA-dependent RNA polymerase (RdRp) inhibition or viral protease (Mpro/PLpro) inhibition; RNA-targeting therapies like siRNA or ASOs aim to degrade the viral RNA transcript directly.