SARS-CoV-2 non-structural protein 16 2′-O-methyltransferase (Nsp16)

SARS-CoV-2 non-structural protein 16 (Nsp16) is a 2′-O-methyltransferase (2′-O-MTase) that plays a pivotal role in the viral life cycle by modifying the 5′ end of viral mRNA [1, 2]. In complex with its essential cofactor Nsp10, Nsp16 catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to the 2′-O-ribose position of the first nucleotide of the mRNA cap structure, converting Cap-0 to Cap-1 [3, 4]. This modification is a sophisticated immune evasion strategy that allows viral RNA to mimic host mRNA, thereby avoiding detection by cytoplasmic innate immune sensors such as MDA5 and IFIT proteins [1, 7]. By preventing the activation of the host's type I interferon response, Nsp16 ensures efficient viral replication and protein synthesis [2, 8]. Due to its high conservation across coronaviruses and its critical role in pathogenesis, Nsp16 is considered a prime target for the development of broad-spectrum antiviral therapeutics [4, 6]. Small molecule inhibitors targeting the SAM-binding pocket or the Nsp10-Nsp16 interface aim to restore the host's ability to recognize and clear the virus [3, 5].

Other names

2′-O-methyltransferase2′-O-MTasemRNA cap 2′-O-methyltransferasensp16non-structural protein 16SARS-CoV-2 Nsp16 2′-O-methyltransferase

Inhibition of the 2′-O-methylation of the viral mRNA cap, preventing the conversion of Cap-0 to Cap-1, which leads to the recognition of viral RNA by host innate immune sensors (e.g., MDA5, IFIT1) and subsequent viral clearance [1, 2, 3].