Potentiating effect of ribavirin on the anti-retrovirus activity of 3'-azido-2,6-diaminopurine-2',3'-dideoxyriboside in vitro and in vivo.
3'-Azido-2,6-diaminopurine-2',3'-dideoxyriboside (AzddDAPR) is a potent and selective inhibitor of human immunodeficiency virus (HIV) replication in vitro. It also inhibits Moloney murine sarcoma virus (MSV)-induced transformation of murine C3H/3T3 embryo fibroblasts. AzddDAPR causes a marked dose-dependent suppression of MSV-induced tumor formation and mortality therewith associated in newborn mice infected with MSV. Combination of AzddDAPR with ribavirin resulted in a marked potentiation of its anti-retrovirus activity in vitro and a significant enhancement of its inhibitory effect on MSV-induced tumor formation in vivo. A slight increase in the in vivo toxicity of AzddDAPR was noted when combined with ribavirin.
Balzarini
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Herdewijn
P
P
De Clercq
E
E
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004357:Drug Synergism; D006678:HIV / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008980:Moloney murine sarcoma virus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D012254:Ribavirin / Q000494:pharmacology*; D012263:Ribonucleosides / Q000494:pharmacology*; D009053:Sarcoma Viruses, Murine / Q000187:drug effects*; D012513:Sarcoma, Experimental / Q000473:pathology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D012263:Ribonucleosides; C055319:3'-azido-2,6-diaminopurine-2',3'-dideoxyriboside; D012254:Ribavirin; D016048:Dideoxyadenosine