Department of Virology, Universitätsklinikum Freiburg, Germany.
Methods. 2011 Oct;55(2):188-91. doi: 10.1016/j.ymeth.2011.08.007. Epub 2011 Aug 16.
Due to their ability to rapidly mutate, influenza viruses quickly develop resistance against many antiviral substances, leading to an urgent need for new compounds. The trimeric viral polymerase complex, a major target for the development of new inhibitors, must be assembled from the PB1, PB2, and PA subunits for successful infection. Here, we describe ELISA-based assays which allow the identification of peptides which impair polymerase complex formation. Since the protein-protein interaction domains of the viral polymerase are highly conserved, these inhibitors are also predicted to be active against a broad range of influenza strains. Using this method, identification of small molecules and lead compounds against influenza A and B viruses should be feasible.
由于其快速突变的能力,流感病毒很快就会对许多抗病毒物质产生耐药性,因此迫切需要新的化合物。三聚体病毒聚合酶复合物是开发新抑制剂的主要靶点,为了成功感染,它必须由 PB1、PB2 和 PA 亚基组装而成。在这里,我们描述了基于 ELISA 的测定法,这些测定法可以鉴定出破坏聚合酶复合物形成的肽。由于病毒聚合酶的蛋白-蛋白相互作用域高度保守,因此这些抑制剂也预计对广泛的流感株具有活性。使用这种方法,应该可以鉴定出针对甲型和乙型流感病毒的小分子和先导化合物。