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Polyoxometalates in AIDS Therapy

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Polyoxometalates: From Platonic Solids to Anti-Retroviral Activity

Part of the book series: Topics in Molecular Organization and Engineering ((MOOE,volume 10))

Abstract

HIV causes a severe depletion of CD4-positive helper T cells, and this predisposes patients to opportunistic infections and malignancies which are the leading reasons for morbidity and mortality in AIDS. The retroviral infection latency and immunological abnormalities in patients might be established by the HIV infection of lymphocytes and monocytes/macrophages. In vitro various compounds have been reported for their ability to inhibit the HIV infection of lymphocytes. Among these and in regard of a large broad spectrum, polyoxometalates were evaluated regarding HIV infection inhibition. Polyoxometalates are polyanionic condensed oligomeric aggregates of transition-metal ions, held together only by metal oxygen bonds. The results of in vitro and in vivo experiments revealed at least two mechanisms of action: (1) a direct inhibition of one (or more) of the phases of the lentiviral biological cycle (binding, fusion, RT and RNase activities), (2) a modulation of the immune capacities (ADCC and NK functions) that might result in an restoration of the defective immune system of AIDS patients. Pharmacokinetic studies have been performed in human or non-human primates with two compounds: HPA-23, and JM-2820. These studies confirm (1) the extravascular distribution and (2) the long half-life of the metabolites of two molecules. To date, HPA-23 is the only polyoxo-metalate for which development ended with clinical investigation. These short-term treatments did not permit to demonstrate any efficacy of in vivo HPA-23 administration. These data constitute preliminary elements to re-evaluate polyxometalates. Indeed, three questions remain to be raised: (1) direct and/or indirect infection inhibition of macrophages, (2) the modulation of the cytokine network and (3) the efficiency of polyoxometalates in long-term treatment.

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  1. Experimental Neuropathogenesis and Neurovirology Laboratory, Commissariat a l’Energie Atomique, DSV/DPTE/SSA, 60-68, avenue de la Division Leclerc, BP. 6, 92265, Fontenay aux Roses Cedex, France

    Pascal Clayette & Dominique Dormont

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  1. Pascal Clayette
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Michael T. Pope Achim Müller

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Clayette, P., Dormont, D. (1994). Polyoxometalates in AIDS Therapy. In: Pope, M.T., Müller, A. (eds) Polyoxometalates: From Platonic Solids to Anti-Retroviral Activity. Topics in Molecular Organization and Engineering, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-0920-8_28

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  • DOI: https://doi.org/10.1007/978-94-011-0920-8_28

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-4397-7

  • Online ISBN: 978-94-011-0920-8

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