Oxathiin carboxanilide, a potent inhibitor of human immunodeficiency virus reproduction
Autor: | W. A. Harrison, James B. McMahon, S F Stinson, J. B. Pierce, John P. Bader, V L Narayanan, Owen S. Weislow, M. R. Boyd, R. J. Schultz, C. F. Midelfort |
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Rok vydání: | 1991 |
Předmět: |
Multidisciplinary
Drug Evaluation Preclinical virus diseases HIV Protease Inhibitors Biology Virus Replication Virology Antiviral Agents Reverse transcriptase Virus Cell Line Cell killing Viral replication Cell culture Cricetinae Toxicity CD4 Antigens HIV-1 HIV Protease Inhibitor Animals Humans Reverse Transcriptase Inhibitors Carboxin Cytotoxicity Research Article |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 88(15) |
ISSN: | 0027-8424 |
Popis: | Oxathiin carboxanilide (OC), NSC 615985, a compound originally synthesized as a potential fungicide, was demonstrated to be highly active in preventing human immunodeficiency virus (HIV)-induced cell killing and in inhibiting HIV reproduction. Virus-infected CD4+ lymphocytes were completely protected by 0.5 microM OC, whereas no toxicity was observed at concentrations below 50 microM OC. Production of infectious virus, viral p24 antigen, and virion reverse transcriptase were reduced by OC at concentrations that prevented viral cell killing. A variety of CD4+ T-cell lines were protected by OC from HIV cytopathicity, and OC inhibited two distinct strains of HIV-1. However, HIV-2 infections were unaffected by OC. OC had no direct effect on virions of HIV or on the enzymatic activities of HIV reverse transcriptase or HIV protease. Time-limited treatments of cells with OC before, during, or after exposure of cells to virus failed to protect cells from the eventual cytopathic effects of HIV, and OC failed to inhibit the production of virus from cells in which infection was established or from chronically infected cells. We conclude that the highly active OC has a reversible effect on some early stage of HIV-1 reproduction and cytopathicity. Pilot in vivo experiments showed that circulating concentrations of OC exceeding 1 microM could be achieved and sustained in hamsters for at least a week with no remarkable toxicological sequelae. OC represents a new class of anti-HIV agents that are promising candidates for drug development. |
Databáze: | OpenAIRE |
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