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Evaluation of anti-human immunodeficiency virus activity of maraviroc combined with sifuvirtide in vitro |
BEN Yin-Yin, ZHU Jin-Yu, XU Jian-Qing, ZHANG Xiao-Yan |
Shanghai Public Health Clinical Center,Shanghai 201508, China |
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Abstract 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-bl 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.
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Received: 18 October 2014
Published: 25 April 2015
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Corresponding Authors:
ZHANG Xiao-Yan
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