Saquinavir inhibits the malaria parasite's chloroquine resistance transporter.

Antimicrobial Agents and Chemotherapy
Rowena E MartinTina 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.

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Citations

Jul 31, 2013·Immunology Letters·Rodolfo ThoméLiana Verinaud
Jun 6, 2014·ACS Medicinal Chemistry Letters·Karen J DeaneRussell A Barrow
Dec 12, 2013·The Biochemical Journal·Kiaran Kirk, Adele M Lehane
Nov 19, 2014·Bioscience Reports·Rongwei TengKiaran Kirk
Sep 30, 2015·The American Journal of Tropical Medicine and Hygiene·Siwalee RattanapunyaKesara Na-Bangchang
Aug 9, 2020·Nature Communications·Sarah H ShafikRowena E Martin
Apr 11, 2018·Frontiers in Chemistry·Anna MeierEric Beitz
Dec 22, 2020·ACS Pharmacology & Translational Science·Megan R AnsbroRichard T Eastman

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