2'-O-ribose methyltransferase (nsp16) (nsp16)

SARS-CoV-2 Non-structural protein 16 (nsp16) is a 2'-O-ribose methyltransferase essential for the viral life cycle and immune evasion. It functions by methylating the 5' cap of viral messenger RNA, converting the Cap-0 structure to a Cap-1 structure using S-adenosyl-L-methionine (SAM) as a methyl donor [1, 6]. This modification mimics host mRNA, allowing the virus to escape detection by innate immune sensors such as MDA5 and IFIT1, which would otherwise trigger an antiviral interferon response [4, 16]. Nsp16 is only enzymatically active when complexed with its cofactor, nsp10, which stabilizes the SAM-binding pocket and extends the RNA-binding groove [9, 10]. As a critical component of the viral replication-transcription complex, nsp16 is a high-priority target for antiviral drug development [7, 8]. Potential therapeutic strategies include the use of SAM-competitive inhibitors, such as sinefungin, or small molecules that disrupt the nsp10-nsp16 protein-protein interaction [2, 3, 16]. Inhibiting nsp16 not only halts viral replication but also restores the host's ability to mount an effective immune response against the infection [1, 16].

Other names

nsp162'-O-MTaseRNA-cap 2'-O-methyltransferaseNon-structural protein 16SARS-CoV-2 nsp16

Inhibition of 2'-O-methyltransferase activity, preventing the conversion of viral mRNA Cap-0 to Cap-1, thereby exposing the virus to host innate immune detection by sensors like MDA5 and IFIT1.