ABSTRACT
Prophylactic administration of a nontoxic dose of 9-[[2-benzyloxyl-1-(benzyloxymethyl)ethoxy]methyl]-6-chlo roguanine (BIOLF-70) to mice reduced the number of myocarditic lesions induced by coxsackievirus B3 (CVB3). BIOLF-70 exhibited minimal antiviral activity against CVB3 in HeLa cells and murine neonatal skin fibroblasts and minimally reduced CVB3 yields in heart tissues. The drug had no effect on serum anti-CVB3 neutralizing antibody titers and did not induce the production of interferon. Flow microfluorometric analyses of splenic lymphocytes taken from BIOLF-70-treated, CVB3-inoculated mice at 7 days postinoculation showed that the proportion of T lymphocytes was increased, as measured by fluorescent staining of Thy-1 and Lyt-2 surface markers, compared with the proportion of T lymphocytes in splenic cells from virus-inoculated or BIOLF-70-treated or normal groups of mice. Splenic lymphocytes from BIOLF-70-treated, CVB3-inoculated mice showed reduced cytotoxic activity against CVB3-infected target fibroblasts. Splenic cells from BIOLF-70-treated, CVB3-inoculated mice had slightly higher natural killer cell activity than did those from the other three groups of mice, which had comparatively similar levels of natural killer cell activity. The data suggest that BIOLF-70 exerts antimyocarditic activity perhaps by some antiviral activity in heart tissues and by immunomodulatory mechanisms which appear to involve T suppressor or T cytotoxic lymphocyte subpopulations and natural killer cells.
Subject(s)
Antiviral Agents/therapeutic use , Coxsackievirus Infections/drug therapy , Guanine/analogs & derivatives , Myocarditis/drug therapy , Animals , Antibodies, Viral/analysis , Coxsackievirus Infections/immunology , Coxsackievirus Infections/pathology , Enterovirus B, Human/drug effects , Enterovirus B, Human/immunology , Guanine/pharmacology , Guanine/therapeutic use , HeLa Cells , Humans , Interferons/metabolism , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Mice , Myocarditis/etiology , Myocardium/pathology , Spectrometry, Fluorescence , Spleen/cytology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Cytotoxic/immunology , Thymidine/metabolismABSTRACT
A new acyclic nucleoside, 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine (BIOLF-62), was found to be efficacious in the treatment of experimental ocular herpes simplex virus infections in rabbits. Complete healing of herpetic lesions occurred in a majority of animals after six days of topical treatment, three times per day. No toxic effects were observed in uninfected, drug-treated eyes. The BIOLF-62 treatment blocked viral replication in infected eyes sufficiently to make recovery of virus from any of the drug-treated eyes impossible, whereas virus was recovered from all placebo-treated eyes.
Subject(s)
Acyclovir/analogs & derivatives , Antiviral Agents/therapeutic use , Keratitis, Dendritic/drug therapy , Acyclovir/therapeutic use , Acyclovir/toxicity , Animals , Antiviral Agents/toxicity , Cornea/pathology , Drug Evaluation, Preclinical , Eye/microbiology , Ganciclovir , Keratitis, Dendritic/microbiology , Keratitis, Dendritic/pathology , Male , Rabbits , Simplexvirus/isolation & purificationABSTRACT
9-[[2-Hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (BIOLF-62) is highly synergistic with either phosphonoformate or phosphonoacetate when used in combination against herpes simplex virus types 1 and 2 in vitro. Acycloguanosine did not show significant synergism with these two compounds. Bromovinyldeoxyuridine and phosphonoformate were highly synergistic against herpes simplex virus type 2, but not against type 1.
