Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, July 2005, p. 2983-2985, Vol. 49, No. 7
0066-4804/05/$08.00+0 doi:10.1128/AAC.49.7.2983-2985.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Antimalarial Activity of Human Immunodeficiency Virus Type 1 Protease Inhibitors
Sunil Parikh,1*
Jiri Gut,1
Eva Istvan,2
Daniel E. Goldberg,2
Diane V. Havlir,1 and
Philip J. Rosenthal1
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, 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 21 January 2005/
Returned for modification 9 March 2005/
Accepted 18 March 2005
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 µM) 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 µM). These findings suggest that use of HIV-1 protease inhibitors may offer clinically relevant antimalarial activity.
* Corresponding author. Mailing address: University of California, San Francisco, Box 0811, San Francisco, CA 94110. Phone: (415) 206-8687. Fax: (415) 648-8425. E-mail:
sunil{at}itsa.ucsf.edu.
Antimicrobial Agents and Chemotherapy, July 2005, p. 2983-2985, Vol. 49, No. 7
0066-4804/05/$08.00+0 doi:10.1128/AAC.49.7.2983-2985.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Lek-Uthai, U., Suwanarusk, R., Ruengweerayut, R., Skinner-Adams, T. S., Nosten, F., Gardiner, D. L., Boonma, P., Piera, K. A., Andrews, K. T., MacHunter, B., McCarthy, J. S., Anstey, N. M., Price, R. N., Russell, B.
(2008). Stronger Activity of Human Immunodeficiency Virus Type 1 Protease Inhibitors against Clinical Isolates of Plasmodium vivax than against Those of P. falciparum. Antimicrob. Agents Chemother.
52: 2435-2441
[Abstract]
[Full Text]
-
He, Z., Qin, L., Chen, L., Peng, N., You, J., Chen, X.
(2008). Synergy of Human Immunodeficiency Virus Protease Inhibitors with Chloroquine against Plasmodium falciparum In Vitro and Plasmodium chabaudi In Vivo. Antimicrob. Agents Chemother.
52: 2653-2656
[Abstract]
[Full Text]
-
Brentlinger, P. E., Behrens, C. B., Kublin, J. G.
(2007). Challenges in the Prevention, Diagnosis, and Treatment of Malaria in Human Immunodeficiency Virus Infected Adults in Sub-Saharan Africa. Arch Intern Med
167: 1827-1836
[Abstract]
[Full Text]
-
Skinner-Adams, T. S., Andrews, K. T., Melville, L., McCarthy, J., Gardiner, D. L.
(2007). Synergistic Interactions of the Antiretroviral Protease Inhibitors Saquinavir and Ritonavir with Chloroquine and Mefloquine against Plasmodium falciparum In Vitro. Antimicrob. Agents Chemother.
51: 759-762
[Abstract]
[Full Text]
-
Parikh, S., Liu, J., Sijwali, P., Gut, J., Goldberg, D. E., Rosenthal, P. J.
(2006). Antimalarial effects of human immunodeficiency virus type 1 protease inhibitors differ from those of the aspartic protease inhibitor pepstatin.. Antimicrob. Agents Chemother.
50: 2207-2209
[Abstract]
[Full Text]
-
Andrews, K. T., Fairlie, D. P., Madala, P. K., Ray, J., Wyatt, D. M., Hilton, P. M., Melville, L. A., Beattie, L., Gardiner, D. L., Reid, R. C., Stoermer, M. J., Skinner-Adams, T., Berry, C., McCarthy, J. S.
(2006). Potencies of Human Immunodeficiency Virus Protease Inhibitors In Vitro against Plasmodium falciparum and In Vivo against Murine Malaria. Antimicrob. Agents Chemother.
50: 639-648
[Abstract]
[Full Text]
-
(2005). A New Use for HIV PIs: Treatment of Malaria?. JWatch Infect. Diseases
2005: 3-3
[Full Text]