The nonstructural protein (nsp) 14 of SARS-CoV 2 was identified as a cap (guanine-N7)-methyltransferase (N7-MTase). Nsp14 of coronaviruses two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. It may be involved in the proof-reading ability during the viral RNA replication and transcription. GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG could be methylated by nsp14.
The guanine-N7 methyltransferase domain of vaccinia virus mRNA capping enzyme is a heterodimer composed of a catalytic subunit and a stimulatory subunit. Cap (guanine-N7) methylation is an essential step in eukaryal mRNA synthesis and a potential target for antiviral, antifungal, and antiprotozoal drug discovery.