Antiviral effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine against cytomegalovirus infection in a guinea pig model.
The antiviral activity of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) against guinea pig cytomegalovirus (GPCMV) was evaluated in guinea pig cell cultures and in Hartley guinea pigs. The 50% effective dose of DHPG against GPCMV replication in cell cultures was 71 microM. Ultrastructural studies revealed that DHPG inhibited the formation of viral cores and the production of nucleocapsids, enveloped virions and dense bodies, but the drug did not prevent the formation of virus induced intranuclear tubular structures. In vivo, guinea pigs inoculated intraperitoneally with GPCMV were treated with DHPG, 25 mg/kg subcutaneously, twice daily. Treatment was initiated 24 h after infection and continued for 7 days. During the acute infection, the average body weights of DHPG-treated, virus infected guinea pigs were approximately 14% lower than the sham-treated counterparts on day 10, 11 and 13 post-virus inoculation. Virus infectivity titers were higher in the lungs of DHPG-treated guinea pigs on day 10 than the sham-treated ones. Although there was no significant difference on histopathologic lesions in the spleen, liver and lungs of the drug-treated and the sham-treated guinea pigs, DHPG treated animals appeared to have fewer virus-induced lesions or inclusions in the kidneys and salivary glands than the sham-treated ones. In addition, virus infectivity titers in the salivary gland of DHPG treated guinea pigs were consistently lower than the sham-treated animals.
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000382:microbiology; D003588:Cytopathogenic Effect, Viral; D015774:Ganciclovir; D006168:Guinea Pigs; D008854:Microscopy, Electron; D009024:Morphogenesis / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015774:Ganciclovir; D000212:Acyclovir