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Biological Impacts of MicroRNAs in Covid-19: Implications for Anti-Viral miRNA-Based Therapies

机译:微小RORNA在Covid-19中的生物学影响:对抗病毒MiRNA的疗法的影响

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Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a novel sever pathogenic coronavirus (CoVs) causing coronavirus disease 2019 (COVID-19), which has become an international concern due to the outbreak and crucial health burden worldwide. SARS-CoV-2 belongs to Coronaviridae family, which are positive single-stranded RNA and contains the largest RNA genome in viruses (1). Interestingly, miRNAs are small non-coding regulator RNAs that involved in various biologic and pathologic processes such as inflammatory responses as well as viral infection. It has been shown that miR-9, miR-98, miR-223, and miR214 expression in CoVs-infected host cells could be changed and subsequently leads to modification in cytokines production (2). miRNA-target prediction via bioinformatics analysis revealed that miR-5197-3p could interact with SARS-CoV-2 gRNA, which could not target any genes in the human genome (3). Therefore, miRNA-based therapy could be proposed for SARS-CoV-2 treatment through the viral genome suppression. In this line, a comparative viral genome analysis showed that six host miRNAs, including let-7a, miR-101, miR-126, miR-23b, miR-378, and miR-98 might be considered as anti-viralmiRNAs which could suppress SARS-CoV-2 target genes including nonstructural protein (nsp), nucleocapsid and spike glycoprotein that (4). Based on our analysis through the VIRmiRNA database, the most of virus-derived miRNAs involved in IFNβ related pathway. COVID-19 treatment with IFNβ, especially in the early stage of the disease, has a beneficial effect in patients (5). PANTHER (protein annotation through evolutionary relationship) analysis indicated that SARS-CoV-2-derived putative miRNAs might inhibit transcription factors and regulators such as STAT1 (6). Suppression of STAT1 expression as a major anti-viral mediator in the IFN signaling pathway by SARS-CoV ORF6 protein suggests that IFN treatment could be more effectiveness in COVID-19 patients (7). Zhi Liu et al., performed computational approaches demonstrated that SARS-CoV-2-derived MR-147-3p via inhibition of transmembrane protease, serine 2 (TMPRSS2) enhances the viral spike (S) priming as the predicted target of miR-4661-3p which facilitates the virus entry into the gastrointestinal tract (8). In addition, gastrointestinal symptoms are associated with poor prognosis in COVID-19 patients. Although these results are preliminary and experimental attempts are inevitable for better pre-clinical and clinical assessment of COVID-19. In summary, it can be concluded that cost and time benefits in silico analysis of virus and/or host miRNAs as well as the target genes network would be a valuable point of view to figure out the underlying molecular mechanisms of COVID-19. Moreover, virus or host genome scanning may lead to discover the promising targets in order to control viral pathogenicity with antiviral miRNA-based therapies.
机译:严重急性呼吸综合征冠状病毒2(SARS-COV-2)是服务器致病的冠状病毒(COVS)一种新型冠状病毒引起的疾病2019(COVID-19),这已成为国际关注,因为爆发和关键医疗负担全世界。 SARS-CoV的-2属于冠状病毒科,其为正单链RNA和含有病毒的最大RNA基因组(1)。有趣的是,miRNA是小的非编码调节RNA,其参与各种生物和病理过程,如炎症反应以及病毒感染。已经示出了miR-9,的miR-98,的miR-223,和在COVS感染的宿主细胞中表达miR214可以在细胞因子的生产(2)改变,并且随后导致修饰。通过生物信息学分析的miRNA靶标预测揭示的miR-5197-3p可以与SARS-CoV的-2 gRNA,这可能无法定位在人类基因组(3)的任何基因相互作用。因此,基于miRNA的疗法可以提出用于通过病毒基因组中抑制SARS-CoV的-2治疗。在这一行,比较病毒基因组分析表明六个主机的miRNA,包括让-7A,的miR-101,miR126的,的miR-23B,的miR-378和miR-98可能被视为反viralmiRNAs这可能抑制SARS-CoV的-2靶基因,包括非结构蛋白(NSP),核衣壳和刺突糖蛋白的是(4)。基于通过VIRmiRNA数据库我们的分析,大多数参与干扰素β相关途径病毒衍生的miRNA。 COVID-19与IFNβ治疗,特别是在疾病的早期阶段,在患者具有有益的作用(5)。 PANTHER(通过进化关系蛋白质注释)分析表明,SARS冠状病毒-2衍生的推定的miRNA可能抑制转录因子和调节剂如STAT1(6)。 STAT1表达的抑制为在SARS-CoV的ORF6蛋白的IFN信号传导途径的主要抗病毒介表明IFN治疗可COVID-19例(7)中更有效性。挚留等,进行显示,计算方法SARS-CoV的-2衍生MR-147-3p经由抑制跨膜蛋白酶,丝氨酸2(TMPRSS2)增强了病毒刺突(S)作为引发的miR-4661的预测的目标-3p这有利于病毒进入胃肠道(8)。此外,胃肠道症状,预后差COVID-19例有关。虽然这些结果是初步的,实验性的尝试都不可避免的COVID-19更好的临床前和临床评估。总之,可以断定,在病毒和/或主机的miRNA的计算机分析以及靶基因网络的成本和时间的好处将是视可贵之处找出COVID-19的潜在分子机制。此外,病毒或宿主基因组扫描可能会发现,以控制病毒的致病性抗病毒基于miRNA的疗法有希望的目标。

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