Aspartic Proteases of Plasmodium falciparum as the Target of HIV-1 Protease Inhibitors

    Clinica delle Malattie Infettive, Università Cattolica
    Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Roma, Italy

    We read with great interest the brief report by Skinner-Adams et al. [1] with regard to the capacity of some HIV-1 protease inhibitors (PIs) to inhibit the growth of Plasmodium falciparum in vitro at clinically achievable and relevant concentrations. Their results are particularly interesting to us, because we have recently obtained strong evidence that the PIs saquinavir, ritonavir, and indinavir, besides exerting antiplasmodial activity in vitro, are also active in a murine model of malaria (A. Savarino, A. Sannella, R. Spaccapelo, M. Dell'Agli, T. Dottorini, G. Galli, C. Severini, E. Bosisio, J. R. Boelaert, A. Crisanti, G. Majori, A. Cassone, and R. Cauda, unpublished data). Nonetheless, we are rather surprised by the statement made by Skinner-Adams et al. that a database search of the P. falciparum genome did not lead to the identification of any plasmodial homologue of the HIV-1 protease.

    References

    1.  Skinner-Adams TS, McCarthy JS, Gardiner DL, Hilton PM, Andrews KT. Antiretrovirals as antimalarial agents. J Infect Dis 2004; 190:19982000. First citation in article

    2.  Tacconelli E, Savarino A, De Bernardis F, Cauda R, Cassone A. Candidiasis and HIV-protease inhibitors: the expected and the unexpected. Curr Med ChemImmun Endoc Metab Agents 2004; 4:4959. First citation in article

    3.  Cassone A, Tacconelli E, De Bernardis F, et al. Antiretroviral therapy with protease inhibitors has an early, immune reconstitutionindependent beneficial effect on Candida virulence and oral candidiasis in human immunodeficiency virusinfected subjects . J Infect Dis 2002; 185:18895. First citation in article