Adaptive Flexible Sialylated Nanogels as Highly Potent Influenza A Virus Inhibitors.,Angewandte Chemie International Edition

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Adaptive Flexible Sialylated Nanogels as Highly Potent Influenza A Virus Inhibitors.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-05-22 , DOI: 10.1002/anie.202006145
Sumati Bhatia ₁ , Malte Hilsch ₂ , Jose Luis Cuellar-Camacho ₁ , Kai Ludwig ₃ , Chuanxiong Nie ₁ , Badri Parshad ₁ , Matthias Wallert ₁ , Stephan Block ₁ , Daniel Lauster ₁ , Christoph Böttcher ₃ , Andreas Herrmann ₂ , Rainer Haag ₁

Affiliation

Flexible multivalent 3D nanosystems that can deform and adapt onto the virus surface via specific ligand–receptor multivalent interactions can efficiently block virus adhesion onto the cell. We here report on the synthesis of a 250 nm sized flexible sialylated nanogel that adapts onto the influenza A virus (IAV) surface via multivalent binding of its sialic acid (SA) residues with hemagglutinin spike proteins on the virus surface. We could demonstrate that the high flexibility of sialylated nanogel improves IAV inhibition by 400 times as compared to a rigid sialylated nanogel in the hemagglutination inhibition assay. The flexible sialylated nanogel efficiently inhibits the influenza A/X31 (H3N2) infection with IC₅₀ values in low picomolar concentrations and also blocks the virus entry into MDCK‐II cells.

中文翻译：

自适应柔性唾液酸化纳米凝胶作为高效甲型流感病毒抑制剂。

灵活的多价 3D 纳米系统可以通过特定的配体-受体多价相互作用变形并适应病毒表面，可以有效阻止病毒粘附到细胞上。我们在这里报告了一种 250 nm 大小的柔性唾液酸化纳米凝胶的合成，该纳米凝胶通过其唾液酸 (SA) 残基与病毒表面上的血凝素刺突蛋白的多价结合来适应甲型流感病毒 (IAV) 表面。我们可以证明，在血凝抑制试验中，与刚性唾液酸化纳米凝胶相比，唾液酸化纳米凝胶的高灵活性将 IAV 抑制提高了 400 倍。柔性唾液酸化纳米凝胶可在低皮摩尔浓度下有效抑制甲型/X31 (H3N2) 流感病毒感染（IC ₅₀值），并阻止病毒进入 MDCK-II 细胞。

更新日期：2020-07-13

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