沙奎那韦抑制疟原虫的氯喹耐药转运蛋白。
Saquinavir inhibits the malaria parasite's chloroquine resistance transporter.
机构信息
Research School of Biology, The Australian National University, Canberra, ACT, Australia.
出版信息
Antimicrob Agents Chemother. 2012 May;56(5):2283-9. doi: 10.1128/AAC.00166-12. Epub 2012 Feb 21.
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.
摘要
抗逆转录病毒蛋白酶抑制剂（APIs）利托那韦、沙奎那韦和洛匹那韦，用于治疗 HIV 感染，在临床相关浓度下抑制疟原虫生长。此外，据报道，这些 API 在体外增强了氯喹（CQ）对这种寄生虫的活性。这种作用的机制尚不清楚，但不同 API 之间的化学增敏程度不同，除了利托那韦之外，似乎还依赖于寄生虫表现出 CQ 耐药表型。在这里，我们使用表达不同 PfCRT 等位基因的转基因寄生虫和非洲爪蟾卵母细胞系统进行 PfCRT 的异源表达，研究了 PfCRT 在 CQ 和 APIs 相互作用中的作用。我们的数据表明，沙奎那韦表现为 CQ 耐药逆转剂，这至少部分解释了它增强 CQ 在 CQ 耐药疟原虫中的作用的能力。
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