Antiviral effect of oxetanocin G against guinea pig cytomegalovirus infection in vitro and in vivo.
The antiviral activity of a new guanosine analog, 9-(2-deoxy-2-hydroxymethyl-beta-D-erythrooxetanosyl)guanine (OXT-G), against guinea pig cytomegalovirus (GPCMV) was evaluated both in vitro and in vivo. In the plaque reduction assay, the median effective concentration (EC50) of OXT-G, ganciclovir (DHPG) and acyclovir (ACV) against GPCMV was 0.03, 6.4 and 52 micrograms/ml, respectively. The selectivity index, based on the ratio of the median inhibitory concentration for cell growth of guinea pig embryo fibroblasts to the median effective concentration for GPCMV plaque formation, was about 100-fold higher than that of DHPG. In an in vivo study, Hartley guinea pigs infected with GPCMV were treated with OXT-G or DHPG (20 mg/kg/day) for 2 weeks, and it was found that virus titers in the salivary gland were 70-fold lower in OXT-G-treated guinea pigs than in DHPG-treated animals. The results indicate that OXT-G was more potent and selective against GPCMV infection than DHPG.
Yamamoto
N
N
Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Japan.
Yamada
Y
Y
Daikoku
T
T
Nishiyama
Y
Y
Tsutsui
Y
Y
Shimada
N
N
Takahashi
K
K
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D005347:Fibroblasts; D015774:Ganciclovir / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006168:Guinea Pigs; D006801:Humans; D009500:Neutralization Tests; D012469:Salivary Glands / Q000382:microbiology
D000998:Antiviral Agents; C057479:oxetanocin G; D006147:Guanine; D015774:Ganciclovir; D000212:Acyclovir