Mass spectrometric based detection of protein nucleotidylation in the RNA polymerase of SARS-CoV-2

SARS-CoV-2 RNA-dependent RNA polymerase (RdRp; nsp12) contains N-terminal NiRAN domain that possesses a nucleotidyl transferase activity. The lysine 2 in SARS-CoV-2 nsp7 was demonstrated to be a nucleotidylation site mediated by the nsp12 NiRAN. The RdRp of SARS-CoV-2 is a complex of nsp7, nsp8 and nsp12. The nucleotidylated site of nsp7 locates in the binding interface with nsp8 and nsp12, suggesting that the nucleotidylation may be involved in the formation of the optimal polymerase complex.