Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus
Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus
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DOI：
10.1179/2047773212y.0000000004
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发表时间：
2012-03-01
影响因子：
3.4
通讯作者：
Superti, Fabiana
中科院分区：
文献类型：
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作者：
Ammendolia, Maria Grazia;Agamennone, Mariangela;Superti, Fabiana
牛乳铁蛋白（bLf）是一种多功能糖蛋白，在抗感染（包括流感）的先天免疫中起重要作用。在这里，我们将bLf分解为C-叶和n -叶，并表明流感病毒血凝和细胞感染的抑制完全归因于C-叶，并且包括H1N1和H3N2在内的所有主要病毒亚型都受到抑制。通过远西印迹和测序研究，我们证明bLf C- lobe与病毒血凝素的HA(2)区域紧密结合，正是包含融合肽的高度保守区域。通过分子对接研究，鉴定出3个C-lobe片段，在5摩尔浓度范围内抑制病毒血凝和感染。除了有助于解释bLf广泛的抗流感活性外，我们的发现还为开发bLf片段作为潜在抗流感治疗药物的来源奠定了基础。
Bovine lactoferrin (bLf) is a multifunctional glycoprotein that plays an important role in innate immunity against infections, including influenza. Here we have dissected bLf into its C- and N-lobes and show that inhibition of influenza virus hemagglutination and cell infection is entirely attributable to the C- lobe and that all major virus subtypes, including H1N1 and H3N2, are inhibited. By far-western blotting and sequencing studies, we demonstrate that bLf C- lobe strongly binds to the HA(2) region of viral hemagglutinin, precisely the highly conserved region containing the fusion peptide. By molecular docking studies, three C-lobe fragments were identified which inhibited virus hemagglutination and infection at fentomolar concentration range. Besides contributing to explain the broad anti-influenza activity of bLf, our findings lay the foundations for exploiting bLf fragments as source of potential anti-influenza therapeutics.