Unique spectrum of activity of 9-[(1,3-dihydroxy-2-propoxy)methyl]-guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1.
A guanosine analog, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG), was found to inhibit herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, cytomegalovirus, and Epstein-Barr virus replication by greater than 50% at concentrations that do not inhibit cell growth in culture. The potency of the drug against all of these viruses is greater than that of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir). DHPG was active against HSV-1 growth during the early phase of virus replication and had no activity when added at a later time after infection. Its antiviral activity was irreversible. Thymidine partially neutralized its action. The anti-HSV-1 activity of DHPG was dependent on the induction and the properties of virus-induced thymidine kinase. Virus variants that induced altered virus thymidine kinase and became resistant to acyclovir were still as sensitive to DHPG as the parental virus. DHPG is active against five different HSV variants with induced altered DNA polymerase and resistance to acyclovir.
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D015774:Ganciclovir; D006564:Herpesviridae / Q000187:drug effects* / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018139:Simplexvirus / Q000187:drug effects*; D013937:Thymidine Kinase / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase; D015774:Ganciclovir; D000212:Acyclovir