New gamma-substituted analogues of dNTP were synthesized and their enzymatic stability and antiviral properties were evaluated.

Dinucleoside 5',5''-oligophosphates d(Np 4 N'), dTp 3 rA, dTp 4 rA , and dTp 5 rA were synthesized and evaluated as substrates for HIV reverse transcriptase, the Klenow fragment of E. coli DNA polymerase I, and E. coli RNA polymerase. A model of the HIV reverse transcriptase interaction with the dinucleoside oligophosphates was proposed and experimentally confirmed. The kinetic constants of some of the synthesized compounds for the HIV reverse transcriptase were determined.

Association of deletion polymorphism in GSTT1 and GSTM1 genes and polymorphic variant A313G of GSTP1 gene with cirrhosis diseases and 4-year survival rate for the Tomsk region (West Siberia) patients were tested. Homozygous deletion of GSTM1 gene (null genotype) was a protective factor for alcoholic and mixed (HCV, HBV and alcohol) liver cirrhosis development. The patients from the joint group (all etiology forms) as well as having alcoholic and mixed cirrhosis had lower frequency of GSTM1 null genotype (39.2, 39.0, and 34.2%, respectively) in comparison with the control group (64.6%). The GSTM1 null genotype and GSTP1 gene A313G polymorphic variant correlated with the patients' survival rate. The patients survived in comparison with the dead had higher frequency of a GSTM1 null genotype (46.6 vs. 30.2%) and GSTP1 AA genotype (63.1 vs. 40.5%), and lower frequency of GSTP1 AG (A313G) genotype (31.1 vs. 51.2%). A survival rate was 2.5 times higher for patients having GSTP1 AA genotype in comparison with the GG and AG genotype carriers and 2 times higher for patients having GSTM1 null genotype than the gene carriers. A 4-year fatal case probability was 2.3 times higher among the patients having heterozygous AG GSTP1 genotype in comparison with homozygous AA and GG genotype carriers.

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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.