Important note: Information in this article was accurate in 1987. The state of the art may have changed since the publication date.
PROSPECTS FOR CHEMOTHERAPEUTIC OR CHEMOPROPHYLACTIC INTERVENTION IN AIDS-RELATED RETROVIRUS INFECTION
Animal Models of Retrovirus Infection and Their Relationship to AIDS. Salzman LA, ed. Orlando, Florida, Academic Press, p. 241-64, 1986.. Unique Identifier : AIDSLINE ICDB/87629280 Shannon WM; Kettering-Meyer Lab., Southern Res. Inst., Birmingham, AL
Abstract:
The prospects for chemotherapeutic intervention and possibly even chemoprophylaxis in the control of acquired immune deficiency syndrome (AIDS) virus infection are discussed. Most of the research efforts in antiviral chemotherapy in recent yr have been directed toward the herpes viruses. The chemical structures of selected purine and pyrimidine nucleoside analogs that have demonstrated significant activity against the herpes viruses are shown in a figure. These compounds are activated in the infected cell by the herpes virus-induced deoxypyrimidine kinase. Of these compounds, acyclovir has been licensed by the Food and Drug Administration for use in primary genital herpes and mucocutaneous herpes in the immunosuppressed host. 9-beta-D-Arabinofuranosyladenine (araA) has been examined for antiviral activity in a plaque reduction test; Gross or Rauscher murine leukemia virus (MLV) replication in mouse embryo cells was found to be inhibited in a dose-dependent manner. When the araA was tested in vivo, it was found to significantly inhibit Rauscher virus-induced tumorigenesis. Cyclaradine, a carbocyclic analog of araA, is quite effective against herpes virus infections; it is as effective as acyclovir in the treatment of genital herpes virus infections in the guinea pig model. Another promising compound that has been shown to have activity against MLV is ribavirin; the activity of ribavirin against Gross and Rauscher leukemia viruses both in vitro and in vivo was demonstrated. Phosphonoacetic acid (PAA), a DNA polymerase inhibitor that inhibits herpes virus replication, has also been found to significantly inhibit MLV replication in cell culture and to inhibit MLV reverse transcriptase in a dose-dependent manner. PAA acts as a noncompetitive inhibitor of the DNA polymerase by interacting with the enzyme at the pyrophosphate binding site. Treatment of Rauscher virus-infected mice with pyrazofurin resulted in significant inhibition of splenomegaly in these animals. Some of these various compounds could have clinically useful activity against human AIDS-related retroviruses. (23 Refs)
Keywords: Acquired Immunodeficiency Syndrome/*DRUG THERAPY Animal Antiviral Agents/*THERAPEUTIC USE Arabinonucleosides/PHARMACOLOGY/THERAPEUTIC USE AIDS-Related Complex/*DRUG THERAPY DNA, Viral/BIOSYNTHESIS Herpesviridae Infections/DRUG THERAPY Human Mice Phosphonoacetic Acid/THERAPEUTIC USE Pyrimidine Nucleosides/*THERAPEUTIC USE Retroviridae Infections/DRUG THERAPY Reverse Transcriptase/ANTAGONISTS & INHIB Ribavirin/THERAPEUTIC USE Ribonucleosides/THERAPEUTIC USE Rifamycins/THERAPEUTIC USE Vidarabine/ANALOGS & DERIVATIVES/THERAPEUTIC USE Virus Replication/DRUG EFFECTS MONOGRAPH
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Important note: Information in this article was accurate in 1987. The state of the art may have changed since the publication date.
