A calorimetric study of 3d metal ions-Acyclovir / Aciclovir interactions. The 2-hydroxyethoxymethyl group of Acyclovir / Aciclovir mimics the role of ribose in deoxy-guanosine and guanosine promoting the coordination through N(7).

The equilibrium constants and enthalpic values of metal Acyclovir / Aciclovir complexes have been determined by calorimetry for Co(II) (log K=0.96+/-0.05, DeltaH (kJ/mol)=-19.7+/-1.3), Ni(II) (log K=1.39+/-0.03, DeltaH (kJ/mol)=-21.5+/-1.0), Cu(II) (log K=1.83+/-0.03, DeltaH (kJ/mol)=-23.2+/-0.8) and Zn(II) (log K=0.71+/-0.06, DeltaH (kJ/mol)=-18.6+/-1.5). The equilibrium constants are similar to those of the divalent ions with guanosine and 2,9-dimethylpurine. By comparison with previous thermodynamic data, it can be shown that the 2-hydroxyethoxymethyl group promotes coordination through N(7) versus N(1) of the guanine ring for 3d metal ions. These results reveal that the 2-hydroxyethoxymethyl group placed on the purine ring of guanine in Acyclovir / Aciclovir causes a greater effect than that of the 9-methyl in purines and similar to or greater than that of the ribose moiety in guanosine. The 2-hydroxyethyoxymethyl group of Acyclovir / Aciclovir mimics the role of ribose in deoxy-guanosine and guanosine promoting a similar coordination chemistry (with very close log K and DeltaH values) for Acyclovir / Aciclovir, deoxy-guanosine and guanosine with divalent metals.

Prevention of herpes simplex virus infection and latency by prophylactic treatment with Acyclovir / Aciclovir in a weanling mouse model.

OBJECTIVE: Acyclovir / Aciclovir is an antiviral agent that inhibits acute herpes simplex virus replication and decreases the frequency of reactivation, but it is not currently used to prevent primary disease or the establishment of latency. The purpose of this study was to reexamine the efficacy of Acyclovir / Aciclovir in preventing acute and latent herpes simplex virus infection. STUDY DESIGN: Mice were infected by footpad inoculation with 2 viral recombinants that express beta-galactosidase. Half of each group was treated prophylactically with intraperitoneal Acyclovir / Aciclovir and then given Acyclovir / Aciclovir in the drinking water. Four days after infection, the dorsal root ganglia were removed, fixed, and stained, and the number of cells expressing beta-galactosidase were counted. RESULTS: Compared with placebo, prophylactic Acyclovir / Aciclovir completely inhibited acute viral replication as evidenced by the absence of beta-galactosidase activity (P < .001) and significantly decreased the number of neurons harboring latent infection (P = .01). CONCLUSION: Acyclovir / Aciclovir prophylaxis prevented acute and reduced latent ganglionic infection with herpes simplex virus in a weanling mouse model.

Effect of antibody alone and combined with Acyclovir / Aciclovir on neonatal herpes simplex virus infection in guinea pigs.

Neonatal herpes simplex virus (HSV) infection produces severe disease with unacceptable morbidity and mortality with current antiviral therapies. The effect of therapy with passive anti-HSV antibody and Acyclovir / Aciclovir was evaluated using a guinea pig model of neonatal HSV. Newborn animals were inoculated intranasally and treated with Acyclovir / Aciclovir (60 mg/kg/day) or antibody (or both), beginning on days 0, 2, or 3 after HSV-2 inoculation. Acyclovir / Aciclovir alone was effective only when begun on day 0, and antibody alone was effective when begun on or before day 2. Only combination therapy was effective on day 3, reducing mortality from 82% (14/17) in controls to 44% (7/16; P < .05). Combined therapy also significantly reduced the duration of skin, eye, and mouth disease and respiratory symptoms but not recurrent disease. These data suggest that addition of antibody therapy to Acyclovir / Aciclovir may improve the outcome of neonatal HSV disease.

Ganciclovir ophthalmic gel in herpes simplex virus rabbit keratitis: intraocular penetration and efficacy.

A chronic administration of three ganciclovir gels (0.2%, 0.05%, 0.0125%) was compared with a placebo gel and a 3% Acyclovir / Aciclovir ophthalmic ointment in the treatment of HSV-1 rabbit keratitis. All the ganciclovir gels showed a clinical efficacy: a significant reduction of the corneal ulcer area, clouding and vascularization (p < 0.05) and a fast inhibition of HSV isolates into tear film with the 0.2% and 0.05% ganciclovir gels. However the efficacy was slower than using Acyclovir / Aciclovir ointment. No significant difference could be shown between the 0.2% and 0.05% ganciclovir gels or the 0.05% ganciclovir gel and the Acyclovir / Aciclovir treatment on viral isolation, when it was performed on pooled samples. The distribution of ganciclovir and Acyclovir / Aciclovir into the rabbit eyes (HPLC methods), were similar but markedly higher in solid tissues than ocular fluids. It might explain the recovery from tissue damages. The mean corneal ganciclovir concentrations were largely higher than ED 50 of ganciclovir for HSV-1. No toxicity was expected, due to very limited systemic availability. This study suggests a comparable activity on HSV-1 superficial keratitis between 0.05%, 0.2% ganciclovir gels and 3% Acyclovir / Aciclovir ointment. Higher concentration of ganciclovir gels are probably necessary in order to treat the HSV-1 kerato-uveitis.