acyclovir and 5--amino-5-iodo-2--5--dideoxyuridine

The molecular basis for the antiviral activity is discussed for a variety of nucleoside compounds approved for clinical use in the U.S.A. (5-iodo-2'-deoxyuridine, 5-trifluoromethyl-2'-deoxyuridine, 9-beta-D-arabinofuranosyladenine, 9-(2-hydroxyethoxymethyl)guanine), or in clinical trial (E-5-(2-bromovinyl)-2'-deoxyuridine, 1-(2-deoxy-2-fluoro-beta-D-arabinosyl)-5-iodocytosine, 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), or of specific interest to our laboratory (5-iodo-5'-amino-2',5'-dideoxyuridine, 5'-amino-5'-deoxythymidine). The consequence of incorporation of idoxuridine, the 5'-amino analog of thymidine or the 5'-amino analog of idoxuridine into the DNA of herpes simplex virus type 1 on transcription and translation is emphasized.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Cytarabine; Dideoxynucleosides; DNA, Viral; Idoxuridine; Protein Biosynthesis; Ribavirin; Simplexvirus; Structure-Activity Relationship; Thymidine; Thymine Nucleotides; Transcription, Genetic; Vidarabine

Topics: Acyclovir; Adenine; Animals; Antiviral Agents; Arabinonucleosides; Bromodeoxyuridine; Chemical Phenomena; Chemistry; Cytarabine; Deoxyuridine; Guanine; Herpesviridae Infections; Humans; Idoxuridine; Nucleosides; Ribavirin; Thymidine; Virus Diseases; Viruses

The therapeutic efficacy of two new antiviral agents, 5-iodo-5'-amino-2', 5'-dideoxyuridine (AIdUrd) and 9-(2-hydroxyethoxymethyl)guanine (ACV), in the model of mouse lip inoculated with herpes simplex virus type 2 is reported. The effects on development of clinical lesions, viral replication in the inoculated lips, and establishment of latent viral infection in the trigeminal ganglia were observed. The earlier the treatment with AIdUrd and ACV was initiated after inoculation, the better was the chemotherapeutic effect. AIdUrd and ACV treatment, when initiated 48 and 72 hr after inoculation, respectively, showed no chemotherapeutic efficacy. Establishment of viral latent infection in sensory ganglia was significantly prevented only when ACV treatment was initiated very early (1 or 3 hr) after inoculation. The results indicate that both drugs have significant antiviral activity, in part dependent on the time of initiation of therapy, and that ACV is superior to AIdUrd as a topical agent for therapy of herpes simplex virus type 2 infections.

Topics: Acyclovir; Animals; Antiviral Agents; Guanine; Herpes Labialis; Idoxuridine; Mice; Rabbits; Stomatitis, Herpetic; Time Factors; Trigeminal Ganglion