丙型肝炎病毒的治疗方法:基于反义寡核苷酸的候选囊壳抑制剂的硅学设计。

IF 1.9 4区 医学 Q3 GENETICS & HEREDITY
Virus Genes Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI:10.1007/s11262-024-02088-1
Burcu Hasturk, Fatih Eren
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引用次数: 0

摘要

直接作用抗病毒(DAA)药物已被证明能有效降低病毒载量,治愈大部分丙型肝炎病毒(HCV)感染。然而,还应考虑到与疗程相关的成本以及任何可能的不良反应。此外,必须承认某些群体可能不符合治疗条件。鉴于目前还没有获准用于治疗 HCV 感染的疫苗,因此需要一种有效、安全且易于获得的治疗方法,这仍然是一个至关重要的优先事项。本研究旨在开发一种基于反义寡核苷酸(ASO)的治疗药物,它可以抑制 HCV 荚膜。利用 NCBI 病毒数据门户分析了 817 个 HCV 荚膜蛋白 mRNA 序列后,在所有基因型(1-7)中发现了一个 7 个核苷酸(nt)的保守区。然而,由于其 GC% 含量较高,该区域并不适合作为 ASO 的靶点。相反,在去除缺失和不同的序列数据后,801 个数据集中保留了另一个仅有 8 nt 长的高度保守区域。然后利用计算机模拟对候选 ASO 进行了研究,以评估其潜力。因此,由 8 nt 组成的 ASO 序列有可能成为抑制 HCV 荚膜的可行治疗靶点。此外,7 nt 序列在所有数据集中都是保守的,可以用其他策略代替基于 ASO 的靶向治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A therapeutic approach for the hepatitis C virus: in silico design of an antisense oligonucleotide-based candidate capsid inhibitor.

A therapeutic approach for the hepatitis C virus: in silico design of an antisense oligonucleotide-based candidate capsid inhibitor.

Direct-acting antiviral (DAA) drugs have been shown to effectively reduce viral load and cure a high proportion of hepatitis C virus (HCV) infections. However, costs associated with the course of therapy and any possible adverse effects should also be considered. It is important to acknowledge, moreover, that certain groups may not be eligible for treatment. Given that there is currently no approved vaccine for HCV infection, the need for an effective, safe, and accessible treatment remains a crucial priority. The aim of this study is to develop an antisense oligonucleotide (ASO)-based therapeutic drug that can inhibit HCV capsid. After analyzing 817 HCV capsid protein mRNA sequences using the NCBI Virus Data Portal, a conserved region of 7 nucleotides (nt) was identified in all genotypes (1-7). However, because of its high GC% content, this region is not a suitable target for ASO. Conversely, the other highly conserved region, which is only 8 nt long, was preserved in 801 datasets after removing missing and differing sequence data. The candidate ASO was then investigated using computer simulations to assess its potential. Thus, it is possible that the ASO sequence consisting of 8 nt could be a viable therapeutic target for the inhibition of HCV capsid. Furthermore, the 7 nt sequence, which is conserved in all datasets, may be targeted using alternative strategies in lieu of ASO-based targeting.

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来源期刊
Virus Genes
Virus Genes 医学-病毒学
CiteScore
3.30
自引率
0.00%
发文量
76
审稿时长
3 months
期刊介绍: Viruses are convenient models for the elucidation of life processes. The study of viruses is again on the cutting edge of biological sciences: systems biology, genomics, proteomics, metagenomics, using the newest most powerful tools. Huge amounts of new details on virus interactions with the cell, other pathogens and the hosts – animal (including human), insect, fungal, plant, bacterial, and archaeal - and their role in infection and disease are forthcoming in perplexing details requiring analysis and comments. Virus Genes is dedicated to the publication of studies on the structure and function of viruses and their genes, the molecular and systems interactions with the host and all applications derived thereof, providing a forum for the analysis of data and discussion of its implications, and the development of new hypotheses.
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