Anti-HIV drugs lopinavir/ritonavir activate bitter taste receptors.
Anti-HIV drugs lopinavir/ritonavir activate bitter taste receptors.
复制标题
抗艾滋病毒药物洛匹那韦/利托那韦可激活苦味受体。
DOI：
10.1093/chemse/bjad035
复制
发表时间：
2023
期刊：
影响因子：
3.5
通讯作者：
Cui,Meng
中科院分区：
文献类型：
--
作者：
Chen,Shurui;Zhou,Xinyi;Lu,Yongcheng;Xu,Keman;Wen,Jiao;Cui,Meng
洛匹那韦和利托那韦（LPV/r）是世界卫生组织推荐用于治疗3岁及以上感染HIV的儿童的主要抗人类免疫缺陷病毒（HIV）药物。这些药物通常以液体制剂形式提供，以帮助无法吞咽片剂的儿童服用。然而，与这些药物相关的强烈苦味可能是依从性的重大障碍，特别是在幼儿中，并且可能危及治疗的有效性。研究表明，适口性差会影响艾滋病毒感染儿童的存活率。因此，开发对儿童更友好的蛋白酶抑制剂制剂，特别是那些味道更好的制剂，对艾滋病毒感染儿童至关重要。洛匹那韦和利托那韦激活苦味受体TAS 2 Rs的分子机制尚不清楚。在这项研究中，我们利用钙动员试验来表征洛匹那韦和利托那韦激活苦味受体。我们发现洛匹那韦激活TAS 2 R1和TAS 2 R13，而利托那韦激活TAS 2 R1、TAS 2 R8、TAS 2 R13和TAS 2 R14。开发以这些受体为靶点的具有安全特性的苦味阻断剂对于消除这些抗HIV药物的令人不快的苦味是非常理想的。
Lopinavir and ritonavir (LPV/r) are the primary anti-human immunodeficiency virus (HIV) drugs recommended by the World Health Organization for treating children aged 3 years and above who are infected with the HIV. These drugs are typically available in liquid formulations to aid in dosing for children who cannot swallow tablets. However, the strong bitter taste associated with these medications can be a significant obstacle to adherence, particularly in young children, and can jeopardize the effectiveness of the treatment. Studies have shown that poor palatability can affect the survival rate of HIV-infected children. Therefore, developing more child-friendly protease inhibitor formulations, particularly those with improved taste, is critical for children with HIV. The molecular mechanism by which lopinavir and ritonavir activate bitter taste receptors, TAS2Rs, is not yet clear. In this study, we utilized a calcium mobilization assay to characterize the activation of bitter taste receptors by lopinavir and ritonavir. We discovered that lopinavir activates TAS2R1 and TAS2R13, while ritonavir activates TAS2R1, TAS2R8, TAS2R13, and TAS2R14. The development of bitter taste blockers that target these receptors with a safe profile would be highly desirable in eliminating the unpleasant bitter taste of these anti-HIV drugs.