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Antimicrobial Agents and Chemotherapy, June 2006, p. 2207-2209, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00022-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Antimalarial Effects of Human Immunodeficiency Virus Type 1 Protease Inhibitors Differ from Those of the Aspartic Protease Inhibitor Pepstatin

Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California,¹ Department of Medicine and Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri²

Received 6 January 2006/ Returned for modification 30 January 2006/ Accepted 6 March 2006

Human immunodeficiency virus type 1 protease inhibitors (HIVPIs) and pepstatin are aspartic protease inhibitors with antimalarial activity. In contrast to pepstatin, HIVPIs were not synergistic with a cysteine protease inhibitor or more active against parasites with the cysteine protease falcipain-2 knocked out than against wild-type parasites. As with pepstatin, HIVPIs were equally active against wild-type parasites and against parasites with the food vacuole plasmepsin aspartic proteases knocked out. The antimalarial mechanism of HIVPIs differs from that of pepstatin.

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