A small fragmented P protein of respiratory syncytial virus inhibits virus infection by targeting P protein.
A small fragmented P protein of respiratory syncytial virus inhibits virus infection by targeting P protein.
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DOI：
10.1099/jgv.0.001350
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发表时间：
2019-11
期刊：
影响因子：
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通讯作者：
K. Hara;Kenichiro Yaita;P. Khamrin;K. Kumthip;T. Kashiwagi;J. Éléouët;M. Rameix-Welti;Hiroshi Watanabe
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作者：
K. Hara;Kenichiro Yaita;P. Khamrin;K. Kumthip;T. Kashiwagi;J. Éléouët;M. Rameix-Welti;Hiroshi Watanabe
多肽类药物在抗病毒治疗中具有广阔的应用前景。在这里，我们研究了来自人类呼吸道合胞病毒(HRSV)核糖核蛋白(RNP)组分的病毒蛋白片段的抗病毒潜力。基于针对病毒蛋白功能区的模拟方法，我们设计了核蛋白(N)、基质蛋白M2-1和磷蛋白(P)的各种片段，并在RSV微型基因组系统中测试了它们的抗病毒活性。我们发现，在P(81个氨基酸长度)C-末端的第130-180和212-241残基的片段(记为P-Fr)通过与全长P的竞争结合而显著抑制聚合酶活性。进一步对P-Fr的缺失分析表明，P-Fr的三个功能结构域(寡聚、L结合和核衣壳结合)是最大抑制活性所必需的。更重要的是，纯化的重组P-Fr在RSV感染的Hep-2细胞中显示出显著的低纳摩尔范围的抗病毒活性。这些结果突出了P作为开发抗RSV和其他副粘病毒化合物的重要靶点。
Peptide-based inhibitors hold promising potential in the development of antiviral therapy. Here, we investigated the antiviral potential of fragmented viral proteins derived from ribonucleoprotein (RNP) components of the human respiratory syncytial virus (HRSV). Based on a mimicking approach that targets the functional domains of viral proteins, we designed various fragments of nucleoprotein (N), matrix protein M2-1 and phosphoprotein (P) and tested the antiviral activity in an RSV mini-genome system. We found that the fragment comprising residues 130-180 and 212-241 in the C-terminal region of P (81 amino acid length), denoted as P Fr, significantly inhibited the polymerase activity through competitive binding to the full-length P. Further deletion analysis of P Fr suggested that three functional domains in P Fr (oligomerization, L-binding and nucleocapsid binding) are required for maximum inhibitory activity. More importantly, a purified recombinant P Fr displayed significant antiviral activity at low nanomolar range in RSV-infected HEp-2 cells. These results highlight P as an important target for the development of antiviral compounds against RSV and other paramyxoviruses.