Topology-Matching Design of an Influenza-Neutralizing Spiky Nanoparticle-Based Inhibitor with a Dual Mode of Action.,Angewandte Chemie International Edition

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Topology-Matching Design of an Influenza-Neutralizing Spiky Nanoparticle-Based Inhibitor with a Dual Mode of Action.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-05-18 , DOI: 10.1002/anie.202004832
Chuanxiong Nie _{1,

2} , Badri Parshad ₃ , Sumati Bhatia ₁ , Chong Cheng ₄ , Marlena Stadtmüller ₂ , Alexander Oehrl ₁ , Yannic Kerkhoff ₁ , Thorsten Wolff ₂ , Rainer Haag ₁

Affiliation

In this study, we demonstrate the concept of “topology‐matching design” for virus inhibitors. With the current knowledge of influenza A virus (IAV), we designed a nanoparticle‐based inhibitor (nano‐inhibitor) that has a matched nanotopology to IAV virions and shows heteromultivalent inhibitory effects on hemagglutinin and neuraminidase. The synthesized nano‐inhibitor can neutralize the viral particle extracellularly and block its attachment and entry to the host cells. The virus replication was significantly reduced by 6 orders of magnitude in the presence of the reverse designed nano‐inhibitors. Even when used 24 hours after the infection, more than 99.999 % inhibition is still achieved, which indicates such a nano‐inhibitor might be a potent antiviral for the treatment of influenza infection.

中文翻译：

具有双重作用模式的流感中和尖峰纳米颗粒抑制剂的拓扑匹配设计。

在这项研究中，我们展示了病毒抑制剂的“拓扑匹配设计”概念。根据目前对甲型流感病毒（IAV）的了解，我们设计了一种基于纳米颗粒的抑制剂（纳米抑制剂），它具有与 IAV 病毒颗粒匹配的纳米拓扑结构，并对血凝素和神经氨酸酶表现出异多价抑制作用。合成的纳米抑制剂可以在细胞外中和病毒颗粒并阻止其附着和进入宿主细胞。在反向设计的纳米抑制剂的存在下，病毒复制显着减少了 6 个数量级。即使在感染后24小时使用，仍然可以实现99.999%以上的抑制，这表明这种纳米抑制剂可能是治疗流感感染的有效抗病毒药物。

更新日期：2020-05-18

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