The antiviral activity of 9-beta-D-arabinofuranosyladenine is enhanced by the 2',3'-dideoxyriboside, the 2',3'-didehydro-2',3'-dideoxyriboside and the 3'-azido-2',3'-dideoxyriboside of 2,6-diaminopurine.
The 2',3'-dideoxyriboside (ddDAPR), 2',3'-didehydro-2',3'-dideoxyriboside (ddeDAPR) and 3'-azido-2',3'-dideoxyriboside (AzddDAPR) of 2,6-diaminopurine have been previously recognized as potent inhibitors of human immunodeficiency virus replication. These compounds are also potent inhibitors of adenosine deaminase and inhibit the deamination of 9-beta-D-arabinofuranosyladenine (araA). ddDAPR, ddeDAPR and AzddDAPR markedly potentiate the antiviral activity of araA against herpes simplex virus type 1 (HSV-1), type 2 (HSV-2) and vaccinia virus (VV). When used at a concentration of 20 micrograms/ml, which had by itself no antiviral effect, ddDAPR, ddeDAPR and AzddDAPR increased the ability of araA to suppress HSV-1, HSV-2 and VV yield by several orders of magnitude. The maximum antiviral effect was obtained with the combinations of ddDAPR or ddeDAPR with araA concentrations of 1 and 10 micrograms/ml.
Balzarini
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
De Clercq
E
E
D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018139:Simplexvirus / Q000187:drug effects* / Q000254:growth & development; D014616:Vaccinia virus / Q000187:drug effects* / Q000254:growth & development; D014740:Vidarabine / Q000008:administration & dosage / Q000494:pharmacology*; D010948:Viral Plaque Assay
D015224:Dideoxynucleosides; C052692:2,6-diaminopurine 2',3'-dideoxyriboside; C052693:2,6-diaminopurine 2',3'-didehydro-2',3'-dideoxyriboside; C055319:3'-azido-2,6-diaminopurine-2',3'-dideoxyriboside; D016048:Dideoxyadenosine; D014740:Vidarabine