A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats
A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats
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DOI：
10.1016/j.bbrc.2012.06.097
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发表时间：
2012-07-27
影响因子：
3.1
通讯作者：
Kodama, Eiichi N.
中科院分区：
文献类型：
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作者：
Li, Xiaoguang;Qian, Hua;Kodama, Eiichi N.
缺乏用于评价抗人类免疫缺陷病毒1型（HIV-1）药物的小动物模型阻碍了药物开发。在这里，我们描述了一个简单而快速的评价系统，在大鼠模型没有动物感染设施的建立。在向大鼠腹膜内施用测试药物后，通过MAGI测定法检查血清中的抗病毒活性。使用HIV-1（IIIB）和HIV-1（BaL）分别作为代表性CXGR 4和CCR 5嗜性HIV-1毒株，评价了最近开发的HIV-1进入抑制剂，两种CXCR 4拮抗剂TF 14016和FC 131，以及四种融合抑制剂T-20、T-20 EK、SC 29 EK和TRI-1144。在大鼠血清中，CXCR 4拮抗剂仅显示具有抗HIV-1（IIIB）活性，而融合抑制剂显示抗HIV-1（IIIB）和抗HIV-1（BaL）活性。这些结果表明，试验药物被成功地处理到大鼠血清中，并且可以通过MAGI测定法进行检测。在该系统中，TRI-1144显示出最有效和持续的抗病毒活性。未给药动物的血清显示出显著的抗HIV-1活性，表明可能需要相对较高剂量或活性的试验药物。总之，本研究建立的大鼠表型药物评价新体系，可用于多种抗病毒药物的体内评价。(C)2012 Elsevier Inc. All rights reserved.
The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1(IIIB) and HIV-1(BaL) as representative CXGR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1(IIIB) activity, whereas fusion inhibitors showed both anti-HIV-1(IIIB) and anti-HIV-1(BaL) activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, "phenotypic drug evaluation", may be applicable for the evaluation of various antiviral drugs in vivo. (C) 2012 Elsevier Inc. All rights reserved.