Inhibitory activity of S-adenosylhomocysteine hydrolase inhibitors against human cytomegalovirus replication

Antiviral Res. 1993 Jul;21(3):197-216. doi: 10.1016/0166-3542(93)90028-h.


Various acyclic and carbocyclic adenosine analogues, which are apparently targeted at the S-adenosylhomocysteine (AdoHcy) hydrolase have been reported to inhibit the replication of a number of pox-, rhabdo-, paramyxo-, arena-, and reoviruses. Here we show that this activity spectrum extends to human cytomegalovirus (HCMV). Of the compounds tested, neplanocin A, 3-deazaneplanocin A, 6'-C-methylneplanocin A and 5'-noraristeromycin were found to be the most potent inhibitors of HCMV replication in vitro. Their 50% inhibitory concentration ranged from 0.05 to 1.35 micrograms/ml. In general, the anti-HCMV activity of the adenosine analogues correlated well with their affinity (Ki) for AdoHcy hydrolase, suggesting that AdoHcy hydrolase may be considered as a target enzyme for anti-HCMV agents. For four compounds (3-deazaneplanocin A, 6'-C-methylneplanocin A (isomers I and II) and 3-deazaadenosine), anti-HCMV potency was greater than could be expected solely from their interaction with AdoHcy hydrolase, suggesting that these compounds may be functioning by an additional mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology*
  • Adenosylhomocysteinase
  • Antiviral Agents / pharmacology*
  • Cells, Cultured
  • Cesium
  • Chlorides
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / physiology
  • Fluorescent Antibody Technique
  • Humans
  • Hydrolases / antagonists & inhibitors*
  • Molecular Structure
  • Virus Replication / drug effects


  • Antiviral Agents
  • Chlorides
  • Cesium
  • Hydrolases
  • Adenosylhomocysteinase
  • cesium chloride
  • Adenosine