Antimalarial activity of human immunodeficiency virus type 1 protease inhibitors.
Aspartic proteases play key roles in the biology of malaria parasites and human immunodeficiency virus type 1 (HIV-1). We tested the activity of seven HIV-1 protease inhibitors against cultured Plasmodium falciparum. All compounds inhibited the development of parasites at pharmacologically relevant concentrations. The most potent compound, lopinavir, was active against parasites (50% inhibitory concentration [IC50], 0.9 to 2.1 microM) at concentrations well below those achieved by ritonavir-boosted lopinavir therapy. Lopinavir also inhibited the P. falciparum aspartic protease plasmepsin II at a similar concentration (IC50, 2.7 microM). These findings suggest that use of HIV-1 protease inhibitors may offer clinically relevant antimalarial activity.
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, Box 0811, San Francisco, California 94110, USA. sunil@itsa.ucsf.edu
Sunil
S
Parikh
Jiri
J
Gut
Eva
E
Istvan
Daniel E
DE
Goldberg
Diane V
DV
Havlir
Philip J
PJ
Rosenthal
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D003470:Culture Media; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development
D000962:Antimalarials; D003470:Culture Media; D017320:HIV Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin