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抗 H5 亚型禽流感病毒血凝素的抗病毒 RNA 适体的筛选。

Selection of an antiviral RNA aptamer against hemagglutinin of the subtype H5 avian influenza virus.

机构信息

Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea.

出版信息

Nucleic Acid Ther. 2011 Dec;21(6):395-402. doi: 10.1089/nat.2011.0321. Epub 2011 Oct 21.

DOI:10.1089/nat.2011.0321
PMID:22017542
Abstract

Avian influenza is an acute viral respiratory disease caused by RNA viruses of the family Orthomyxoviridae. The influenza A virus subtype H5 can cause severe illness and results in almost 100% mortality rate among livestock. Hemagglutinin (HA) present in the virus envelope plays an essential role in the initiation of viral infection. In this study, we investigated the efficacy of using HA as a target for antiviral therapy through nucleic acid aptamers. After purification of the receptor binding domain (HA1) of HA protein, activity of recombinant HA1 was confirmed by using hemagglutination assay. We selected RNA aptamer candidates after 15 rounds of iterative Systematic Evolution of Ligands by EXponential enrichment (SELEX) targeting the biologically active HA protein. The selected RNA aptamer HAS15-5, which specifically binds to HA1, exhibited significant antiviral efficacy according to the results of a hemagglutination inhibition assay using egg allantoic fluids harboring the virus. Thus, the RNA aptamer HAS15-5, which acts by blocking and inhibiting the receptor-binding domain of viral HA, can be developed as a novel antiviral agent against type H5 avian influenza virus.

摘要

禽流感是一种由正粘病毒科 RNA 病毒引起的急性呼吸道疾病。H5 亚型流感病毒可导致严重疾病,并导致牲畜死亡率接近 100%。病毒包膜中的血凝素(HA)在病毒感染的起始中发挥重要作用。在这项研究中,我们通过核酸适体研究了将 HA 用作抗病毒治疗靶标的效果。在纯化 HA 蛋白的受体结合域(HA1)后,通过血凝试验确认了重组 HA1 的活性。我们针对具有生物活性的 HA 蛋白进行了 15 轮迭代系统进化配体的 EXponential enrichment(SELEX),筛选出 RNA 适体候选物。所选的 RNA 适体 HAS15-5 特异性结合 HA1,根据使用含有病毒的鸡胚尿囊液进行的血凝抑制试验的结果,显示出显著的抗病毒功效。因此,该 RNA 适体 HAS15-5 通过阻断和抑制病毒 HA 的受体结合域起作用,可以开发为针对 H5 型禽流感病毒的新型抗病毒药物。

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