Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs.
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