Carbocyclic analogue of 3-deazaadenosine: a novel antiviral agent using S-adenosylhomocysteine hydrolase as a pharmacological target.

The carbocyclic analogue of 3-deazaadenosine (3-deaza-C-Ado) has been synthesized and found to have antiviral activity in cell culture against herpes simplex virus type 1, vaccinia virus, and HL-23 C-type virus. It is relatively noncytotoxic at effective antiviral concentrations and is not subject to deamination or phosphorylation. It acts as a competitive inhibitor of S-adenosyl-L-homocysteine hydrolase, is at best a poor substrate, and does not inactivate the enzyme significantly. 3-Deaza-C-Ado may cause a selective inhibition of the methylation of the polynucleotide 5' cap of viral mRNA via higher cellular concentrations of S-adenosyl-L-homocysteine, resulting from the inhibition of S-adenosylhomocysteine hydrolase in infected cells, since increases in the intracellular level of S-adenosylhomocysteine, but no effects on DNA or RNA synthesis, were observed after incubation of these cells with it.