ping enzyme (D1-D12) (41 U), human RNA N7 MTase (hRNMT) (50 nM). Compounds were previously dissolved in 100% DMSO. n.i: no inhibition detected at 50 μM.
Unexpectedly, all the bisubstrate compounds were barely active against the 2′-O MTases of flaviviruses or coronavirus SARS-CoV. In contrast, most of the compounds displayed inhibition of N7-MTases. Dinucleoside 2 bearing the amino acid chain of the SAM showed some significant inhibition of both viral N7-MTases with a better activity on Vaccinia D1-D12 than on SARS-CoV nsp14. However, compound 2 also displayed a potent inhibition of hRNMT in the same range as the viral MTases displaying a lack of specificity against human and viral enzymes. The amino acid group of 2 seems essential for inhibition since compound 1 with a non-subst