马纳维诺与西夫韦肽体外联合抗人类免疫缺陷病毒感染的效果评价

Evaluation of anti-human immunodeficiency virus activity of maraviroc combined with sifuvirtide in vitro

本文旨在探讨人类免疫缺陷病毒1型（HIV-1）CC趋化因子受体5（CCR5）辅助受体拮抗剂马纳维诺（MRV）与膜融合抑制剂西夫韦肽（SFT）在抗HIV感染中的协同作用。利用TZM-bl细胞系检测SFT和MRV单用或联用对3种CCR5噬性（SVPB16、SVPC12和CRF01_AE）HIV假病毒的半数有效浓度（EC50）。采用CalcuSyn软件对2种药物的协同性进行预测,联合指数（CI）〈1为有协同作用,CI=1为有相加效应,CI〉1为有拮抗作用。同时,应用噻唑蓝（MTT）法对MRV和SFT的细胞毒性进行评价。结果显示,2种药物单用时对SVPB16、SVPC12和CRF01_AE的EC50：SFT为0.91、0.17、0.71nmol/L,MRV为4.84、0.47、0.45nmol/L。针对这3种假病毒,联用比单用EC50均有所降低,SFT（0.45、0.09、0.15nmol/L）降低1-4倍,MRV（1.52、0.12、0.11nmol/L）降低2-3倍。2种药物联用对3种假病毒抑制率达90%时的CI值分别为0.28、0.59和0.36。等效线法显示两者之间存在良好的协同作用。综上所述,联用MRV与SFT在不产生细胞毒性的情况下具有良好的协同抗HIV效果。

The present paper aims to explore the synergistic effect of maraviroc （MRV） [-an inhibitor of human immunodeficiency virus type 1 （HIV-1） co-receptor chemokine （C-C motif） receptor 5 （CCR5）] and sifuvirtide （SFT） （HIV-1 entry inhibitor） on HIV infection. Three HIV-1 pseudovirus strains including SVPB16, SVPC12 and CRF01_AE subtypes were used to infect TZM-bl cells in vitro. The effects of MRV and SFT, alone or combined, on the HIV-1/TZM-b1 infection system were investigated, and their 50% effective concentration （EC50） values were calculated. The synergistic effect of SFT and MRV was predicted by CalcuSyn software according to the combined index （CI） values. The CI values indicated a synergistic effect when 〈1, an antagonistic effect when 〉1, and an additive effect when equal to 1. The cytotoxic effects of MRV and SFT, alone or combined, were also evaluated by methylthiazolyl tetrazolium （MTT） method. When used alone, the EC50 values of SFT were 0.91, 0.17 and 0.71 nmol/L against SVPB16, SVPC12 and CRF01_AE pseudoviruses, respectively; and the EC50 values of MRV were 4.84, 0.47 and 0.45 nmol/L, respectively. When SFT and MRV were used in combination, the EC50 values of them were reduced by two to four times for SFT （0.45, 0.09 and 0.15 nmol/L）, and two to three times for MRV （1.52, 0.12 and 0.11 nmol/L）. The results calculated by isobologram software indicated that there was a good synergistic effect between SFT and MRV. It is suggested that combination of SFT and MRV has a good synergistic effect on HIV-1 infection in vitro with no significant cell toxicity.