论文部分内容阅读
HIV-1蛋白酶(PR)活性的严格调控对于病毒的生存至关重要。在病毒蛋白表达及病毒颗粒装配过程中,处于病毒前体蛋白Gag-Pol中的蛋白酶必须以无活性状态存在,避免前体蛋白Gag-Pol和Gag被提前酶切加工(前体蛋白早成熟化)。干扰HIV-1蛋白酶活性的调控机制,特异性的激活前体蛋白中的蛋白酶,诱导前体蛋白早成熟化,就可以直接抑制病毒的复制。根据这一设想,运用生物发光共振能量转移技术,建立细胞水平的HIV-1前体蛋白早成熟化激活剂筛选模型,并通过3000个化合物的试验性筛选对筛选模型进行评价。研究结果表明该筛选方法灵敏可靠,特异性高,重复性好(Z’因子为0.905)。
The strict regulation of HIV-1 protease (PR) activity is crucial for the survival of the virus. During viral protein expression and viral particle assembly, proteases in the viral precursor protein Gag-Pol must be present in an inactive state, avoiding premature cleavage of the precursor proteins Gag-Pol and Gag (premature maturation of the precursor protein ). Interfering with the regulatory mechanism of HIV-1 protease activity, specifically activating the protease in the precursor protein, inducing early maturation of the precursor protein, can directly inhibit the replication of the virus. Based on this idea, a bioluminescence resonance energy transfer technique was used to establish a cell-level screening model for early maturation activator of HIV-1 precursor protein. The screening model was evaluated by experimental screening of 3000 compounds. The results show that the screening method is sensitive, specific and reproducible (Z ’factor 0.905).