nsp16nsp10

nsp16nsp10 refers to the functional complex formed by coronavirus non-structural proteins 16 and 10. Nsp16 is a S-adenosyl-L-methionine-dependent 2'-O-methyltransferase that modifies the 2'-OH of the first nucleotide of the viral mRNA cap, producing Cap-1 from Cap-0, a modification essential for efficient translation and immune evasion.

On its own, nsp16 shows limited catalytic activity; binding of nsp10 stimulates its activity by stabilizing the active site and promoting substrate binding. Together, the nsp16-nsp10 complex methylates the RNA cap in the replication-transcription complex within the cytoplasm, using SAM as methyl donor.

Structural and biochemical studies in SARS-CoV-1 and SARS-CoV-2 show a conserved heterodimer with a defined interface; nsp10 acts as a cofactor, and the complex interacts with the cap structure and RNA substrate to catalyze 2'-O-methylation required for Cap-1 formation.

Biological significance of the complex lies in its role in viral RNA capping, which helps viral mRNA mimic host mRNA and reduces detection by innate immune sensors such as IFIT proteins and MDA5. Disruption of the nsp16-nsp10 complex can impair viral replication and enhance interferon responses, underscoring its importance in viral fitness.

Genetically, nsp16 and nsp10 are produced from the coronavirus ORF1a/1b polyproteins and mature through proteolytic processing to become part of the larger replication-transcription complex.

Clinically, the essential nature of 2'-O-methylation makes the nsp16-nsp10 interface and the catalytic pocket attractive targets for antiviral drug development, with approaches including SAM-competitive inhibitors and compounds that disrupt the protein–protein interaction.