摘要：The rapid growth of the global hiv/AIDS epidemic makes it a high priority to develop an effective *** a live attenuated or inactivated hiv vaccine is not likely to be approved for clinical application due to safety concerns,hiv virus like particles(VLPs) offer an attractive alternative because they are considered safer since they lack viral *** got a stable eukaryotic cell line by G418 resistance selection,engineered to express the hiv-1 structure protein Gag and Env efficiently and *** confirmed the presence of Gag and Env proteins in the cell culture supernatant and that they could self-assemble into *** VLPs were found to be able to elicit specific humoral and cellular immune response after immunization without any adjuvant.

摘要：In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines(NP-DATAs),synthesis of a series of novel biphenyl-substituted diaryltriazines(BP-DATAs)with a flexible side chain attached at the C-6 position is *** compounds exhibited excellent potency against wild-type(WT)hiv-1 with EC50 values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of hiv-1 mutant *** 5 j and 6 k had the best activity against WT,single and double hiv-1 mutants and reverse transcriptase(RT)enzyme comparable to two reference drugs(EFV and ETR)and our lead compound NP-DATA(1).Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the hiv-1 reverse transcriptase non-nucleoside binding pocket(NNIBP)attributing to the improved *** preliminary structure-activity relationship and PK profiles were also discussed.

摘要：An effective hiv-1 vaccine will be the ultimate solution for the prevention of hiv/AIDS, though HAART plays important roles in treating the disease. In this study, a large-scale recombinant DNA plasmid containing a designed hiv-1 multi-epitope- p24 chimeric gene was prepared and purified. Rhesus monkeys were then inoculated muscularly with the plasmid for four times in week 0, 4, 8 and 18. Whole blood was collected two weeks after the third and fourth inoculation, followed by serum and pe- ripheral blood mononuclear cell (PBMC) separation. The CTL activity and proliferation of PBMCs stimu- lated by macaque MHC-I-restricted hiv-1 CTL epi- tope peptide were analyzed by MTT and LDH release assay, respectively. Th1 cytokines in supernatant of cultured PBMC stimulated by hiv-1 CTL epitope peptide and anti-hiv-1 antibody in serum were as- sayed by ELISA. The results showed that increased CTL target-killing activity, higher secretion of Th1 cytokines (IFN-γ and IL-2) and promoted proliferative reaction of monkey PBMCs stimulated by hiv-1 CTL epitope peptide were detected in the immunization group inoculated by the recombinant DNA vaccine for three times, which were further enhanced by the fourth inoculation. At the same time, hiv-1 specific antibody in serum of immunized monkeys was higher than that in controls. We concluded that the designedhiv-1 DNA vaccine may induce hiv-1 specific cellular and humoral immunity on monkeys.

摘要：为了设计以hiv-1跨膜蛋白gp41为靶点的抑制剂,采用分子对接、分子动力学模拟及自由能计算方法研究了gp41与其抑制剂NB-2的结合模式,利用从头药物设计方法,通过改造NB-2的结构,设计了有效的gp41选择性抑制剂,并用分子对接方法评价了这些新化合物的结合模式和能力.从分子对接结果得到2种主要的NB-2与gp41的结合模式.分子动力学模拟和自由能计算结果表明,结合模式1优于模式2,所以模式1是比较合理的结合模式.从结合模式1出发设计了103个新的化合物,这些化合物具有已知gp41抑制剂所没有的结构特征且大部分化合物比NB-2与gp41的结合自由能低.得到的结合模式合理解释了NB-2与gp41的相互作用.

摘要：目的综述了hiv1侵入细胞的机制及近年来hiv1侵入细胞抑制剂的研究现状。方法以近几年国内外有代表性的论文为依据,进行分析、整理和归纳。结果与结论hiv1侵入靶细胞是一个多步过程,主要包括病毒吸附,协同受体结合,膜融合。针对这一过程设计的药物,可有效地阻断hiv1侵入细胞,从而抑制病毒的感染。

摘要：艾滋病已给人类社会和经济带来了巨大影响。文章以hiv-1膜融合糖蛋白gp41的C端序列为参照,设计合成了C22多肽的基因序列,经PCR放大以后,通过pTMHa30-51质粒转导进*** BL21(DE3)中进行表达,纯化后得到了C22多肽,表达产物经SDS-PAGE电泳分析和质谱验证。结果表明:C22多肽具有很好热稳定性,良好的hiv-1入侵细胞抑制活性和水溶性,在实验浓度下对细胞无毒性。通过圆二色谱技术对C22的二级结构进行了检测,C22溶液在37℃条件下,α螺旋比例增加,而在80℃条件下,α螺旋比例则呈下降趋势。在不同pH值条件下,C22峰值变化较大,在向酸碱两性方向变化时,C22的α螺旋结构比例均相对有所减少,无规则卷曲增加,结构趋向松散。这也表明,在pH 6条件下,C22可以保持相对稳定的结构。该研究为此类多肽的光谱学性质研究和设计新的hiv-1治疗药物提供了理论基础。

摘要：目的综述hiv-1RNase H的生化作用及以该酶为靶点的hiv-1抑制剂的药物设计、构效关系和作用机制等方面的研究进展。方法着重以近几年国外该领域有代表性的文献为依据,进行分析、归纳、总结。结果与结论RNase H在hiv-1逆转录过程中发挥着十分重要的作用,针对该酶所设计的抑制剂,可有效地抑制hiv-1的复制,因此hiv-1RNase H是抗艾滋病治疗中的一个有潜力的药物作用靶点。

摘要：在hiv-1(human immunodeficiency virus type 1)的复制周期中,逆转录酶(reverse transcriptase,RT)和整合酶(integrase,IN)均发挥着非常重要的作用,它们一直是抗hiv药物研究的热门靶点。逆转录酶抑制剂(RT inhibitors)是目前临床上治疗艾滋病(AIDS)患者和hiv感染者的一线药物,而整合酶抑制剂(IN inhibitors)新近也有药物上市,两方面的单独研究均取得了可喜的成果。近年来,多靶点药物研究策略渐渐引起科研工作者的浓厚兴趣,经过合理药物设计及随机筛选发现了多类具有hiv逆转录酶和整合酶双重抑制活性的化合物。本文主要就hiv逆转录酶和整合酶双靶点抑制剂的发现与结构修饰的最新研究进展进行介绍,以期对抗hiv药物研究有所启示。

摘要：hiv-1(human immunodeficiency virus type 1)病毒感染因子Vif(viral infectivity factor)是高度保守的碱性磷酸化蛋白质,是hiv-1的辅助调节蛋白之一。Vif蛋白的主要功能是能够介导宿主细胞体内载脂蛋白BmRNA编辑酶催化多肽样蛋白3G(apolipoprotein B mRNA editing enzyme catalytic polypeptide like 3G,APOBEC3G)的降解,从而增强病毒的感染性。此外,它还具有调节病毒的逆转录和复制晚期以及诱导细胞G2期停滞等功能。目前,许多实验室已经针对Vif蛋白进行抑制剂的设计。本文简要叙述了Vif蛋白的结构与功能,并主要对其抑制剂的最新进展进行了综述。

摘要：艾滋病主要是由人免疫缺陷病毒I型(human immunodeficiency virus type 1,hiv-1)感染引起的全身性免疫功能丧失综合征。hiv-1核壳体蛋白7(nucleocapsid protein 7,NCp7)在病毒的逆转录过程和整合过程都发挥着重要作用。由于NCp7的保守性,基于此靶点的抑制剂不易产生耐药性。本综述介绍了近10年来所报道的hiv-1 NCp7抑制剂的研究新进展。