PDF(Pubmed)
Abstract：
UNASSIGNED: The naturally occurring dipeptide Tryptophylglycine (WG) is enhanced in human immunodeficiency virus (HIV-1) infected Elite Controllers (EC). We have shown that this dipeptide has an anti-HIV-1 effect and evaluated now its synergistic antiretroviral activity, in combination with current antiretrovirals against multi-drug resistant HIV-1 isolates.
UNASSIGNED: Drug selectivity assay with WG-am and ARVs agains HIV-1 resistant isolates were carried out. Subsequently, two methods, Chou-Talalay\'s Combination Index (CI) and ZIP synergy score (SS), were used to quantify the synergism.
UNASSIGNED: WG-am had a moderate/strong synergism with the four tested antiretrovirals: raltegravir, tenofovir, efavirenz, darunavir. WG-am:TDF had strong synergism at ED50, ED75, ED90 (CI: <0.2) in isolates resistant to protease inhibitors or integrase strand inhibitors (INSTI), and a slightly less synergism in isolates resistant to non-nucleoside or nucleotide reverse transcriptase inhibitors. WG-am combined with each of the four drugs inhibited all drug-resistant isolates with over 95% reduction at maximum concentration tested. The highest selectivity indexes (CC50/ED50) were in INSTI-resistant isolates.
UNASSIGNED: Our data suggest that WG, identified as occurring and enhanced in Elite Controllers has a potential to become a future treatment option in patients with HIV-1 strains resistant to any of the four major categories of anti-HIV-1 compounds.
UNASSIGNED: Drug selectivity assay with WG-am and ARVs agains HIV-1 resistant isolates were carried out. Subsequently, two methods, Chou-Talalay\'s Combination Index (CI) and ZIP synergy score (SS), were used to quantify the synergism.
UNASSIGNED: WG-am had a moderate/strong synergism with the four tested antiretrovirals: raltegravir, tenofovir, efavirenz, darunavir. WG-am:TDF had strong synergism at ED50, ED75, ED90 (CI: <0.2) in isolates resistant to protease inhibitors or integrase strand inhibitors (INSTI), and a slightly less synergism in isolates resistant to non-nucleoside or nucleotide reverse transcriptase inhibitors. WG-am combined with each of the four drugs inhibited all drug-resistant isolates with over 95% reduction at maximum concentration tested. The highest selectivity indexes (CC50/ED50) were in INSTI-resistant isolates.
UNASSIGNED: Our data suggest that WG, identified as occurring and enhanced in Elite Controllers has a potential to become a future treatment option in patients with HIV-1 strains resistant to any of the four major categories of anti-HIV-1 compounds.
摘要：
■在人类免疫缺陷病毒（HIV-1）感染的精英控制剂（EC）中，天然存在的二肽色氨酸甘氨酸（WG）得到增强。我们已经证明，这种二肽具有抗HIV-1的作用，现在评估其协同抗逆转录病毒活性，与目前针对多药耐药HIV-1分离株的抗逆转录病毒药物联合使用。
■使用WG-am和ARV对HIV-1耐药的分离株进行了药物选择性测定。随后，两种方法，Chou-Talalay的组合指数(CI)和ZIP协同得分(SS)，用于量化协同作用。
■WG-am与四种测试的抗逆转录病毒药物具有中等/强的协同作用：raltegravir，替诺福韦,efavirenz,Darunavir.WG-am：在对蛋白酶抑制剂或整合酶链抑制剂（INSTI）具有抗性的分离株中，TDF在ED50，ED75，ED90（CI：<0.2）具有很强的协同作用，并且在对非核苷或核苷酸逆转录酶抑制剂具有抗性的分离物中的协同作用略低。WG-am与四种药物中的每一种组合抑制了所有耐药分离株，在测试的最大浓度下减少了95％以上。选择性指数（CC50/ED50）最高的是INSTI抗性分离株。
■我们的数据表明，WG，在EliteControllers中确定为发生和增强的，有可能成为对四种主要类别的抗HIV-1化合物具有抗性的HIV-1菌株患者的未来治疗选择。
■使用WG-am和ARV对HIV-1耐药的分离株进行了药物选择性测定。随后，两种方法，Chou-Talalay的组合指数(CI)和ZIP协同得分(SS)，用于量化协同作用。
■WG-am与四种测试的抗逆转录病毒药物具有中等/强的协同作用：raltegravir，替诺福韦,efavirenz,Darunavir.WG-am：在对蛋白酶抑制剂或整合酶链抑制剂（INSTI）具有抗性的分离株中，TDF在ED50，ED75，ED90（CI：<0.2）具有很强的协同作用，并且在对非核苷或核苷酸逆转录酶抑制剂具有抗性的分离物中的协同作用略低。WG-am与四种药物中的每一种组合抑制了所有耐药分离株，在测试的最大浓度下减少了95％以上。选择性指数（CC50/ED50）最高的是INSTI抗性分离株。
■我们的数据表明，WG，在EliteControllers中确定为发生和增强的，有可能成为对四种主要类别的抗HIV-1化合物具有抗性的HIV-1菌株患者的未来治疗选择。
