Aspartic proteases of Plasmodium falciparum as the target of HIV-1 protease inhibitors

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T. Dottorini, G. Galli, C. Severini, E. Bosisio, J. R. Boelaert, A. Crisanti, G. Majori, A. Cassone, and R. Cauda, unpublished data).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.