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Inhibition of influenza virus replication by constrained peptides targetingnucleoprotein.

机译:受约束肽靶向核蛋白的流感病毒复制的抑制作用。

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BACKGROUND: Because of high mutation rates, new drug-resistant viruses arerapidly evolving, thus making the necessary control of influenza virus infection difficult.METHODS: We screened a constrained cysteine-rich peptide library mimickingμ-conotoxins from Conus geographus and a proline-rich peptide library mimickinglebocin 1 and 2 from Bombyx mori by using influenza virus RNA polymerase (PB1,PB2 and PA) and nucleoprotein (NP) as baits.RESULTS: Among the 22 peptides selected from the libraries, we found that theNP-binding proline-rich peptide, PPWCCCSPMKRASPPPAQSDLPATPKCPP, inhibitedinfluenza replicon activity to mean±sd 40.7%±15.8% when expressed as a GFP fusionpeptide in replicon cells. Moreover, when the GFP fusion peptide was transducedinto cells by an HIV-TAT protein transduction domain sequence, the replication ofinfluenza virus A/WSN/33 (WSN) at a multiplicity of infection of 0.01 wasinhibited to 20% and 69% at 12 and 24 h post-infection, respectively. Inaddition, the TAT-GFP fusion peptide was able to slightly protect Balb/c micefrom WSN infection when administrated prior to the infection.CONCLUSIONS: These results suggest the potential of this peptide as the seed ofan anti-influenza drug and reveal the usefulness of the constrained peptidestrategy for generating inhibitors of influenza infection. The results alsosuggest that influenza NP, which is conserved among the influenza A viruses, is agood target for influenza inhibition, despite being the most abundant protein in infected cells.
机译:背景:由于高突变率,新的耐药病毒酸酸盐酸化,从而使得对流感病毒感染的必要控制困难。方法:我们筛选了来自Conus Geographus和脯氨酸富含脯氨酸的约束富含富含毒素的富含毒素的富含毒素通过使用流感病毒RNA聚合酶(PB1,PB2和PA)和核蛋白(NP)作为BAits.Results:从文库中选择的22种肽中,从Bombyx Mori进行Mimickinglebocin 1和2,我们发现那些富含富含脯氨酸富含脯氨酸的脯氨酸的肽中,PPWCCCSPMKRASPPPAQSDLPATPKCPP,抑制inluenza复制品活性为±SD 40.7%±15.8%时表示为复制子细胞中的GFP氟普肽。此外,当通过HIV-TAT蛋白转导结构域序列进行GFP融合肽的转晶型细胞时,在12和24时,在0.01的多重感染中的血压病毒A / WSN / 33(WSN)的复制较多至20%和69% h分别发生后。在感染之前,TAT-GFP融合肽能够略微保护BALB / C小鼠的BALB / C小鼠。结论:这些结果表明这种肽作为抗流感药物种子的潜力,并揭示了约束肽Strategy用于产生流感感染的抑制剂。结果ALSOSUGGOTEST的流感NP在流感病毒中被保守,是流感抑制的Agood靶标,尽管是受感染细胞中最丰富的蛋白质。

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