Sterilization of Drug-Resistant Influenza Virus through Genetic Interference Inspired by Unnatural Amino Acid-Engineered Particles,Advanced Therapeutics

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Sterilization of Drug-Resistant Influenza Virus through Genetic Interference Inspired by Unnatural Amino Acid-Engineered Particles
Advanced Therapeutics ( IF 3.7 ) Pub Date : 2022-07-01 , DOI: 10.1002/adtp.202200069
Xuesheng Wu ₁ , Zhetao Zheng ₁ , Hongmin Chen ₁ , Haishuang Lin ₁ , Yuelin Yang ₁ , Yachao Bai ₁ , Qing Xia ₁

Affiliation

The frequent emergence of drug resistance during the treatment of influenza A virus (IAV) infections highlights a need for effective antiviral countermeasures. Here, this work presents an antiviral method that utilizes unnatural amino acid-engineered drug-resistant (UAA-DR) virus generated through genetic code expansion to combat emerging drug-resistant viruses through genomic segment reassortment to produce sterilized progenies due to artificial amber codons in the viral genome. This work validates in vitro that UAA-DR can provide a broad-spectrum antiviral strategy for several H1N1 strains, different DR-IAV strains, multidrug-resistant (MDR) strains, and even antigenically distant influenza strains (e.g., H3N2). Moreover, a minimum dose of neuraminidase (NA) inhibitors for influenza virus can further enhance the sterilizing effect when combating inhibitor-resistant strains, partly due to the promoted superinfection of unnatural amino acid-modified virus in cellular and animal models. The fact that the antiviral effect of UAA-DR virus cannot be attributed to interferon stimulation and interferon stimulating genes is also investigated. It is anticipated that UAA-engineered virus-like particle can be extended to combat emerging drug-resistant influenza virus and other segmented RNA viruses.

中文翻译：

通过受非天然氨基酸工程粒子启发的遗传干扰对耐药流感病毒进行灭菌

在治疗甲型流感病毒 (IAV) 感染期间经常出现耐药性，这凸显了对有效抗病毒对策的需求。在这里，这项工作提出了一种抗病毒方法，该方法利用通过遗传密码扩展产生的非天然氨基酸工程抗药性 (UAA-DR) 病毒，通过基因组片段重排来对抗新兴的抗药性病毒，从而产生因人工琥珀密码子而产生的无菌后代。病毒基因组。这项工作在体外验证了 UAA-DR 可以为几种 H1N1 毒株、不同的 DR-IAV 毒株、耐多药 (MDR) 毒株，甚至抗原性遥远的流感毒株（例如 H3N2）提供广谱抗病毒策略。而且，在对抗抑制剂耐药株时，最小剂量的流感病毒神经氨酸酶 (NA) 抑制剂可以进一步增强灭菌效果，部分原因是在细胞和动物模型中促进了非天然氨基酸修饰病毒的重复感染。还研究了 UAA-DR 病毒的抗病毒作用不能归因于干扰素刺激和干扰素刺激基因的事实。预计 UAA 工程病毒样颗粒可以扩展到对抗新兴的耐药流感病毒和其他分段 RNA 病毒。还研究了 UAA-DR 病毒的抗病毒作用不能归因于干扰素刺激和干扰素刺激基因的事实。预计 UAA 工程病毒样颗粒可以扩展到对抗新兴的耐药流感病毒和其他分段 RNA 病毒。还研究了 UAA-DR 病毒的抗病毒作用不能归因于干扰素刺激和干扰素刺激基因的事实。预计 UAA 工程病毒样颗粒可以扩展到对抗新兴的耐药流感病毒和其他分段 RNA 病毒。

更新日期：2022-07-01

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