Antiviral activity of maribavir in combination with other drugs active against human cytomegalovirus.
Antiviral activity of maribavir in combination with other drugs active against human cytomegalovirus.
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DOI：
10.1016/j.antiviral.2018.07.013
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发表时间：
2018-09
影响因子：
7.6
通讯作者：
Derakhchan K
中科院分区：
文献类型：
--
作者：
Chou S;Ercolani RJ;Derakhchan K
人巨细胞病毒（CMV）UL97激酶抑制剂Maribavir作为抗病毒治疗正在进行III期临床试验，包括用于标准治疗难治性或耐药性感染。为了评估其与批准的和实验性CMV抗病毒剂以及与mTor抑制剂雷帕霉素（西罗莫司）组合的活性，通过体外棋盘测定法测试药物作用，并使用基于加性相互作用的独立作用定义的三维模型分析数据。检测了基线病毒和代表性耐药突变体。根据95%置信度下的协同作用体积，当针对野生型和突变型病毒进行检测时，Maribavir显示出与膦甲酸、西多福韦、莱特莫韦和GW 275175 X的累加相互作用，与更昔洛韦的拮抗作用较强，与雷帕霉素的协同作用较强，后者表明可能是一种有用的治疗组合。
The human cytomegalovirus (CMV) UL97 kinase inhibitor maribavir is in Phase III clinical trials as antiviral therapy, including use for infections refractory or resistant to standard therapy. To assess its activity in combination with approved and experimental CMV antivirals, and with the mTor inhibitor rapamycin (sirolimus), drug effects were tested by in vitro checkerboard assays and the data were analyzed using a three dimensional model based on an independent effects definition of additive interactions. Baseline virus and representative drug-resistant mutants were tested. According to the volume of synergy at 95% confidence, maribavir showed additive interactions with foscarnet, cidofovir, letermovir and GW275175X when tested against wild type and mutant viruses, strong antagonism with ganciclovir, and strong synergy with rapamycin, the latter suggesting a potentially useful therapeutic combination.
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