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阿留申病病毒(AMDV)的适体靶向可以是抑制病毒复制的有效策略。

Aptamer-targeting of Aleutian mink disease virus (AMDV) can be an effective strategy to inhibit virus replication.

机构信息

Institute for Laboratory Animal Research, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.

Shanghai Laboratory Animal Research Center, Shanghai, 201203, China.

出版信息

Sci Rep. 2021 Feb 25;11(1):4649. doi: 10.1038/s41598-021-84223-8.

Abstract

Aleutian mink disease (AMD), which is caused by Aleutian mink disease virus (AMDV), is an important contagious disease for which no effective vaccine is yet available. AMD causes major economic losses for mink farmers globally and threatens some carnivores such as skunks, genets, foxes and raccoons. Aptamers have exciting potential for the diagnosis and/or treatment of infectious viral diseases, including AMD. Using a magnetic beads-based systemic evolution of ligands by exponential enrichment (SELEX) approach, we have developed aptamers with activity against AMDV after 10 rounds of selection. After incubation with the ADVa012 aptamer (4 μM) for 48 h, the concentration of AMDV in the supernatant of infected cells was 47% lower than in the supernatant of untreated cells, whereas a random library of aptamers has no effect. The half-life of ADVa012 was ~ 32 h, which is significantly longer than that of other aptamers. Sequences and three dimensions structural modeling of selected aptamers indicated that they fold into similar stem-loop structures, which may be a preferred structure for binding to the target protein. The ADVa012 aptamer was shown to have an effective and long-lasting inhibitory effect on viral production in vitro.

摘要

阿留申病(Aleutian mink disease,AMD)由阿留申病病毒(Aleutian mink disease virus,AMDV)引起,是一种重要的传染性疾病,目前尚无有效的疫苗。AMD 给全球的水貂养殖户造成了重大的经济损失,同时也威胁到一些食肉动物,如臭鼬、缟狸、狐狸和浣熊。适体在传染性病毒疾病的诊断和/或治疗方面具有令人兴奋的应用潜力,包括 AMD。我们采用基于磁珠的指数富集配体系统进化(systemic evolution of ligands by exponential enrichment,SELEX)方法,经过 10 轮筛选后得到了针对 AMDV 的活性适体。用 ADVa012 适体(4 μM)孵育 48 h 后,与未处理细胞相比,感染细胞上清液中的 AMDV 浓度降低了 47%,而随机适体文库则没有效果。ADVa012 的半衰期约为 32 h,显著长于其他适体。所选适体的序列和三维结构建模表明,它们折叠成类似的茎环结构,这可能是与靶蛋白结合的首选结构。ADVa012 适体在体外对病毒产生具有有效且持久的抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d40/7907208/b3ec0c208abc/41598_2021_84223_Fig1_HTML.jpg

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