he sulfone. Finally, the common element of all dinucleosides is an adenosine linked to a N-adenosine by the 2′O position. Its contribution is well defined by the formation of intermolecular hydrogen bonds between the adenosine and Gly333 (3′OH), Ile338 (5′OH), Lys336 (N7) and His424 (N1) residues (Fig. 4). All the major interactions maintain 13 in a suitable orientation in the binding site in place of the natural substrate GpppA-RNA. The docking model of 13 is consistent with our inhibition experimental data and high thermal stability of SARS-CoV nsp14 in the presence of the