Study of Antiherpetic Efficiency of Phosphite of Acycloguanosine Ableto Over come the Barrier of Resistance to Acyclovir.
As has been shown previously, phosphite of acycloguanosine (Hp-ACG) exhibits equal efficacy against ACV-sensitive and ACV-resistant HSV-1 strains in cell culture. Intraperitoneal administration of Hp-ACG to model mice with herpetic encephalitis caused by HSV-1 infection was shown to be effective in protecting against death. In the present work, we continue the study of the antiviral efficiency of Hp-ACG against HSV administered non-invasively; namely in vivo, orally and in the form of ointment formulations. It has been first shown that oral administration of Hp-ACG twice daily for five days prevents systemic infection in mice caused by HSV-1. Mortality in the control group of animals was 57%. Administration of Hp-ACG at doses of 600, 800 and 1,000 mg/kg per day significantly increased the survival and median day of death of the animals compared to the placebo-treated control group. A comparative evaluation of the therapeutic efficacy parameters of polyethylene glycol-based ACV ointment and Hp-ACG ointment was carried out after a 5-day course in the model of an experimental cutaneous infection of HSV-1 in guinea pigs. It was found that Hp-ACG has a significant therapeutic effect resulting in a statistically significant reduction in the lesion's surface area and the amount of vesicular structures. The exhibited therapeutic effect of 10% Hp-ACG in ointment form compares well with that of 5% ACG ointment.
D.I. Ivanovsky Institute of Virology (N.F. Gamaleya Research Center of Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation),Gamaleya Str., 16, Moscow, 123098 , Russia.
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Andronova
V.A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Moscow, 119991, Russia.
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Jasko
V.A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Moscow, 119991, Russia.
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Kukhanova
V.A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Moscow, 119991, Russia.
G A
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Galegov
M.M. Shemyakin-Yr.A.Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, Moscow, 117997, Russia.
Yr S
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Skoblov
V.A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Moscow, 119991, Russia.
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Kochetkov
antiviral activity; herpes simplex virus; in vitro; in vivo