Influenza viruses (IVs) have become increasingly resistant to antiviral drugs that target neuraminidase and matrix protein 2 due to gene mutations that alter their drug-binding target protein regions. Consequently, almost all recent IV pandemics have exhibited resistance to commercial antiviral vaccines. To overcome this challenge, an antiviral target is needed that is effective regardless of genetic mutations. In particular, hemagglutinin (HA), a highly conserved surface protein across many IV strains, could be an effective antiviral target as it mediates binding of IVs with host cell receptors, which is crucial for membrane fusion. HA has 6 disulfide bonds that can easily bind with the surfaces of gold nanoparticles. Herein, we fabricated porous gold nanoparticles (PoGNPs) via a surfactant-free emulsion method that exhibited strong affinity for disulfide bonds due to gold–thiol interactions, and provided extensive surface area for these interactions. A remarkable decrease in viral infectivity was demonstrated by increased cell viability results after exposing MDCK cells to various IV strains (H1N1, H3N2, and H9N2) treated with PoGNP. Most of all, the viability of MDCK cells infected with all IV strains increased to 96.8% after PoGNP treatment of the viruses compared to 33.9% cell viability with non-treated viruses. Intracellular viral RNA quantification by real-time RT-PCR also confirmed that PoGNP successfully inhibited viral membrane fusion by blocking the viral entry process through conformational deformation of HA. We believe that the technique described herein can be further developed for PoGNP-utilized antiviral protection as well as metal nanoparticle-based therapy to treat viral infection. Additionally, facile detection of IAV can be achieved by developing PoGNP as a multiplatform for detection of the virus.

中文翻译：

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用于减弱甲型流感病毒传染性的多孔金纳米粒子

由于基因突变改变了它们的药物结合靶蛋白区域，流感病毒 (IV) 对靶向神经氨酸酶和基质蛋白 2 的抗病毒药物的耐药性越来越强。因此，几乎所有最近的 IV 大流行都表现出对商业抗病毒疫苗的耐药性。为了克服这一挑战，需要一种无论基因突变如何都有效的抗病毒靶点。特别是，血凝素 (HA) 是一种在许多 IV 菌株中高度保守的表面蛋白，它可能是一种有效的抗病毒靶点，因为它介导 IV 与宿主细胞受体的结合，这对于膜融合至关重要。HA 有 6 个二硫键，可以很容易地与金纳米粒子的表面结合。在此处，我们通过无表面活性剂乳液法制造了多孔金纳米粒子（PoGNP），由于金-硫醇相互作用，该方法对二硫键表现出很强的亲和力，并为这些相互作用提供了广泛的表面积。将 MDCK 细胞暴露于用 PoGNP 处理的各种 IV 毒株（H1N1、H3N2 和 H9N2）后，细胞活力结果增加，证明病毒感染性显着降低。最重要的是，在对病毒进行 PoGNP 处理后，感染所有 IV 毒株的 MDCK 细胞的存活率增加至 96.8%，而未处理病毒的细胞存活率为 33.9%。通过实时 RT-PCR 进行的细胞内病毒 RNA 定量也证实，PoGNP 通过 HA 的构象变形阻断病毒进入过程，成功抑制了病毒膜融合。我们相信，本文描述的技术可以进一步开发用于利用 PoGNP 的抗病毒保护以及基于金属纳米颗粒的疗法来治疗病毒感染。此外，通过将 PoGNP 开发为用于检测病毒的多平台，可以轻松检测 IAV。