申请人:THE TRUSTEES OF PRINCETON UNIVERSITY
公开号:EP2581081A2
公开(公告)日:2013-04-17
Alterations of certain metabolite concentrations and fluxes that occur in response to viral infection are described. Host cell enzymes in the involved metabolic pathways are selected as targets for intervention; i.e., to restore metabolic flux to disadvantage viral replication, or to further derange metabolic flux resulting in "suicide" of viral-infected cells (but not uninfected cells) in order to limit viral propagation. While any of the enzymes in the relevant metabolic pathway can be selected, pivotal enzymes at key control points in these metabolic pathways are preferred as candidate antiviral drug targets. Inhibitors of these enzymes are used to reverse, or redirect, the effects of the viral infection. Drug candidates are tested for antiviral activity using screening assays in vitro and host cells, as well as in animal models.; Animal models are then used to test efficacy of candidate compounds in preventing and treating viral infections. The antiviral activity of enzyme inhibitors is demonstrated.
描述了病毒感染时某些代谢物浓度和通量的变化。所涉及的代谢途径中的宿主细胞酶被选为干预目标;即恢复代谢通量以不利于病毒复制,或进一步改变代谢通量导致病毒感染细胞(而非未感染细胞)"自杀 "以限制病毒传播。虽然可以选择相关代谢途径中的任何一种酶,但这些代谢途径关键控制点上的关键酶更适合作为候选的抗病毒药物靶点。这些酶的抑制剂可用于逆转或重定向病毒感染的影响。候选药物通过体外和宿主细胞以及动物模型中的筛选试验进行抗病毒活性测试;然后用动物模型测试候选化合物在预防和治疗病毒感染方面的疗效。展示酶抑制剂的抗病毒活性。