A novel preventive strategy against HIV-1 infection: combinatorial use of inhibitors targeting the nucleocapsid and fusion proteins.
A novel preventive strategy against HIV-1 infection: combinatorial use of inhibitors targeting the nucleocapsid and fusion proteins.
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DOI：
10.1038/emi.2017.26
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发表时间：
2017-06-07
影响因子：
13.2
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Yang Y;Zhu J;Hassink M;Jenkins LMM;Wan Y;Appella DH;Xu J;Appella E;Zhang X
同时攻击多个目标的策略在杀微生物剂开发领域值得探索，以对抗HIV-1序列多样性，最大限度地减少耐药变异体的传播。HIV-1核衣壳蛋白(NCp7)的抑制剂S-酰基-2-硫代苯甲酰胺硫酯-10(SAMT10)与融合抑制剂西夫韦肽(SFT)可能发挥协同作用，因为SFT可以在病毒周期的早期阻止病毒融合，而SAMT10可以在后期破坏病毒颗粒。在这项研究中，我们采用体外细胞培养和体外黏膜外植体模型，研究了SAMT10和SFT联合应用对HIV-1感染的影响。每种化合物的一系列剂量都根据其50%有效浓度(EC50)以10倍的系列稀释度进行测试。我们观察了SAMT10和SFT在体外对实验室适应的HIV-1毒株HIV-1IIIB(B亚型，X4)和在中国性传播人群中流行的三种假型病毒(SVPB16(B亚型，R5)，SVPC12(C亚型，R5)和SH1.81(CRF01_AE，R5))的协同作用。在体外研究中，与单独使用SAMT10或SFT与HIV-1IIIB一起使用时，抑制剂组合在结直肠黏膜外植体中的EC50值降低了1.5-2倍。这些结果可能为开发抗HIV-1性传播的杀微生物剂提供一种新的策略。
The strategy of simultaneously attacking multiple targets is worthy of exploration in the field of microbicide development to combat HIV-1 sequence diversity and minimize the transmission of resistant variants. A combination of S-acyl-2-mercaptobenzamide thioester-10 (SAMT10), an inhibitor of the HIV-1 nucleocapsid protein (NCp7), and the fusion inhibitor sifuvirtide (SFT) may exert synergistic effects, since SFT can block viral fusion at an early stage of the viral cycle and SAMT10 can disrupt viral particles at a later stage. In this study, we investigated the effect of the combination of SAMT10 and SFT on HIV-1 infection using in vitro cell culture and ex vivo mucosal explant models. A range of doses for each compound was tested at 10-fold serial dilutions based on their 50% effective concentrations (EC50). We observed a synergistic effect of SAMT10 and SFT in vitro against both the laboratory-adapted HIV-1 strain HIV-1IIIB (subtype B, X4) and three pseudotyped viruses prevalent in Chinese sexually transmitted populations (SVPB16 (subtype B, R5), SVPC12 (subtype C, R5) and SH1.81 (CRF01_AE, R5)). In the ex vivo study, the EC50 values of the inhibitor combinations were reduced 1.5- to 2-fold in colorectal mucosal explants compared to treatment with SAMT10 or SFT alone by using with HIV-1IIIB. These results may provide a novel strategy for microbicide development against HIV-1 sexual transmission.
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影响因子：
14.8
作者：
Jenkins, Lisa M. Miller;Ott, David E.;Hayashi, Ryo;Coren, Lori V.;Wang, Deyun;Xu, Qun;Schito, Marco L.;Inman, John K.;Appella, Daniel H.;Appella, Ettore
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3.7
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影响因子：
15
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通讯作者：
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影响因子：
1.5
作者：
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通讯作者：
Hendrix, Craig W.
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影响因子：
3.7
作者：
Liu A;Yang Y;Liu L;Meng Z;Li L;Qiu C;Xu J;Zhang X
通讯作者：
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