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非编码RNA的潜在用途及靶向严重急性呼吸综合征冠状病毒2(SARS-CoV-2)5'非翻译区的创新治疗策略

Potential use of noncoding RNAs and innovative therapeutic strategies to target the 5'UTR of SARS-CoV-2.

作者信息

Baldassarre Antonella, Paolini Alessandro, Bruno Stefania Paola, Felli Cristina, Tozzi Alberto Eugenio, Masotti Andrea

机构信息

Children's Hospital Bambino Gesù-IRCCS, Research Laboratories; Multifactorial & Complex Phenotype Research Area, V.le di San Paolo 15, Rome 00146, Italy.

出版信息

Epigenomics. 2020 Aug;12(15):1349-1361. doi: 10.2217/epi-2020-0162. Epub 2020 Sep 2.

Abstract

After the increasing number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections all over the world, researchers and clinicians are struggling to find a vaccine or innovative therapeutic strategies to treat this viral infection. The severe acute respiratory syndrome coronavirus infection that occurred in 2002, Middle East respiratory syndrome (MERS) and other more common infectious diseases such as hepatitis C virus, led to the discovery of many RNA-based drugs. Among them, siRNAs and antisense locked nucleic acids have been demonstrated to have effective antiviral effects both in animal models and humans. Owing to the high genomic homology of SARS-CoV-2 and severe acute respiratory syndrome coronavirus (80-82%) the use of these molecules could be employed successfully also to target this emerging coronavirus. Trying to translate this approach to treat COVID-19, we analyzed the common structural features of viral 5'UTR regions that can be targeted by noncoding RNAs and we also identified miRNAs binding sites suitable for designing RNA-based drugs to be employed successfully against SARS-CoV-2.

摘要

在全球范围内严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染病例不断增加之后,研究人员和临床医生正在努力寻找一种疫苗或创新的治疗策略来治疗这种病毒感染。2002年发生的严重急性呼吸综合征冠状病毒感染、中东呼吸综合征(MERS)以及其他更常见的传染病,如丙型肝炎病毒,促使人们发现了许多基于RNA的药物。其中,小干扰RNA(siRNAs)和反义锁核酸已在动物模型和人类中均显示出有效的抗病毒作用。由于SARS-CoV-2与严重急性呼吸综合征冠状病毒具有高度的基因组同源性(80-82%),这些分子也可成功用于靶向这种新出现的冠状病毒。为了尝试将这种方法应用于治疗COVID-19,我们分析了病毒5'非翻译区(UTR)可被非编码RNA靶向的共同结构特征,并且我们还鉴定了适合设计基于RNA的药物以成功对抗SARS-CoV-2的微小RNA(miRNAs)结合位点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75dd/7466951/2dd8f2cde1b5/figure1.jpg

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