Skip to main content
Article thumbnail
Location of Repository

Saquinavir Inhibits the malaria parasite\u27s chloroquine resistance transporter

By Rowena E. Martin, Alice S. Butterworth, Donald L. Gardiner, Kiaran Kirk, James S. McCarthy and Tina S. Skinner-Adams

Abstract

The antiretroviral protease inhibitors (APIs) ritonavir, saquinavir, and lopinavir, used to treat HIV infection, inhibit the growth of Plasmodium falciparum at clinically relevant concentrations. Moreover, it has been reported that these APIs potentiate the activity of chloroquine (CQ) against this parasite in vitro. The mechanism underlying this effect is not understood, but the degree of chemosensitization varies between the different APIs and, with the exception of ritonavir, appears to be dependent on the parasite exhibiting a CQ-resistant phenotype. Here we report a study of the role of the P. falciparum chloroquine resistance transporter (PfCRT) in the interaction between CQ and APIs, using transgenic parasites expressing different PfCRT alleles and using the Xenopus laevis oocyte system for the heterologous expression of PfCRT. Our data demonstrate that saquinavir behaves as a CQ resistance reverser and that this explains, at least in part, its ability to enhance the effects of CQ in CQ-resistant P. falciparum parasites. Copyrigh

Topics: Falciparum in-vitro, Antiretroviral protease inhibitors, Immunodeficiency-virus type-1, Plasmodium-falciparum, 2725 Infectious Diseases, 2736 Pharmacology (medical), 3004 Pharmacology
Publisher: American Society for Microbiology
Year: 2012
DOI identifier: 10.1128/AAC.00166-12
OAI identifier: oai:espace.library.uq.edu.au:UQ:274433

Suggested articles


To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.