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格里菲辛与替诺福韦、马拉韦罗和恩夫韦肽联合治疗 HIV-1 型 C 群的协同作用特征。

Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide against HIV-1 clade C.

机构信息

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.

出版信息

Virology. 2011 Sep 1;417(2):253-8. doi: 10.1016/j.virol.2011.07.004. Epub 2011 Jul 28.

DOI:10.1016/j.virol.2011.07.004
PMID:21802104
Abstract

Griffithsin (GRFT) is possibly the most potent anti-HIV peptide found in natural sources. Due to its potent and broad-spectrum antiviral activity and unique safety profile it has great potential as topical microbicide component. Here, we evaluated various combinations of GRFT against HIV-1 clade B and clade C isolates in primary peripheral blood mononuclear cells (PBMCs) and in CD4(+) MT-4 cells. In all combinations tested, GRFT showed synergistic activity profile with tenofovir, maraviroc and enfuvirtide based on the median effect principle with combination indices (CI) varying between 0.34 and 0.79 at the calculated EC(95) level. Furthermore, the different glycosylation patterns on the viral envelope of clade B and clade C gp120 had no observable effect on the synergistic interactions. Overall, we can conclude that the evaluated two-drug combination increases their antiviral potency and supports further clinical investigations in pre-exposure prophylaxis for GRFT combinations in the context of HIV-1 clade C infection.

摘要

格夫定(GRFT)可能是天然来源中发现的最有效的抗 HIV 肽。由于其强大且广谱的抗病毒活性和独特的安全性,它具有作为局部杀微生物剂成分的巨大潜力。在这里,我们评估了 GRFT 与 HIV-1 B 群和 C 群分离株在原发性外周血单核细胞(PBMC)和 CD4(+)MT-4 细胞中的各种组合。在所有测试的组合中,根据中值效应原理,GRFT 与替诺福韦、马拉韦罗和恩夫韦肽联合具有协同作用,在计算的 EC(95)水平下,组合指数(CI)在 0.34 到 0.79 之间。此外,B 群和 C 群 gp120 病毒包膜上的不同糖基化模式对协同相互作用没有明显影响。总的来说,我们可以得出结论,评估的两药联合增加了它们的抗病毒效力,并支持在 HIV-1 C 群感染背景下进一步进行 GRFT 联合的暴露前预防的临床研究。

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