SARS-CoV-2 ORF1ab polyprotein (ORF1ab)

The SARS-CoV-2 ORF1ab polyprotein is translated directly from the viral genomic RNA and occupies two-thirds of the coronavirus genome[1][7]. It is cleaved into 16 nonstructural proteins (NSPs) essential for viral transcription, genome replication, and modulation of the host immune response[2][7]. Key enzymes generated from ORF1ab include the main protease (Mpro/NSP5), the RNA-dependent RNA polymerase (RdRp/NSP12), and helicase (NSP13), all of which are critical for viral replication and are major therapeutic targets for COVID-19 antivirals[2][7]. The polyprotein's functions also include processing of viral proteins and shutting down host protein synthesis (NSP1), which suppresses immune signaling[3]. Because mutations in ORF1ab can affect viral replication, immune evasion, and drug sensitivity, it is a major focus for monitoring emerging SARS-CoV-2 variants and for antiviral drug development[2][7][1].

Other names

ORF1abpp1ab (polyprotein 1ab)Replicase polyproteinORF1a/bSARS-CoV-2 nonstructural polyprotein

Inhibition of RNA-dependent RNA polymerase (RdRp; NSP12)\nInhibition of main protease (Mpro; NSP5)\nBlockage of viral genome replication and polyprotein processing