Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.
Gene. 2020 Dec 15;762:145057. doi: 10.1016/j.gene.2020.145057. Epub 2020 Aug 15.
COVID-19 is a lurking calamitous disease caused by an unusual virus, SARS-CoV-2, causing massive deaths worldwide. Nonetheless, explicit therapeutic drugs or clinically approved vaccines are not available for COVID-19. Thus, a comprehensive research is crucially needed to decode the pathogenic tools, plausible drug targets, committed to the development of efficient therapy. Host-pathogen interactions via host cellular components is an emerging field of research in this respect. miRNAs have been established as vital players in host-virus interactions. Moreover, viruses have the capability to manoeuvre the host miRNA networks according to their own obligations. Besides protein coding mRNAs, noncoding RNAs might also be targeted in infected cells and viruses can exploit the host miRNA network via ceRNA effect. We have predicted a ceRNA network involving one miRNA (miR-124-3p), one mRNA (Ddx58), one lncRNA (Gm26917) and two circRNAs (Ppp1r10, C330019G07RiK) in SARS-CoV infected cells. We have identified 4 DEGs-Isg15, Ddx58, Oasl1, Usp18 by analyzing a mRNA GEO dataset. There is no notable induction of IFNs and IFN-induced ACE2, significant receptor responsible for S-protein binding mediated viral entry. Pathway enrichment and GO analysis conceded the enrichment of pathways associated with interferon signalling and antiviral-mechanism by IFN-stimulated genes. Further, we have identified 3 noncoding RNAs, playing as potential ceRNAs to the genes associated with immune mechanisms. This integrative analysis has identified noncoding RNAs and their plausible targets, which could effectively enhance the understanding of molecular mechanisms associated with viral infection. However, validation of these targets is further corroborated to determine their therapeutic efficacy.
新型冠状病毒肺炎（COVID-19）是一种由异常病毒 SARS-CoV-2 引起的潜伏性灾难性疾病，在全球范围内造成了大量死亡。然而，目前尚无针对 COVID-19 的明确治疗药物或经临床批准的疫苗。因此，迫切需要进行全面研究，以解码致病工具和可能的药物靶点，致力于开发有效的治疗方法。在这方面，宿主细胞成分的宿主-病原体相互作用是一个新兴的研究领域。miRNA 已被确定为宿主-病毒相互作用中的重要参与者。此外，病毒能够根据自身需求操纵宿主 miRNA 网络。除了编码蛋白质的 mRNAs 外，非编码 RNA 也可能成为感染细胞中的靶标，并且病毒可以通过 ceRNA 效应利用宿主 miRNA 网络。我们预测了一个涉及 miRNA（miR-124-3p）、mRNA（Ddx58）、lncRNA（Gm26917）和 2 个 circRNA（Ppp1r10、C330019G07RiK）的 ceRNA 网络，该网络存在于 SARS-CoV 感染的细胞中。通过分析一个 mRNA GEO 数据集，我们鉴定了 4 个差异表达基因-Isg15、Ddx58、Oasl1、Usp18。没有明显诱导干扰素和 IFN 诱导的 ACE2，ACE2 是介导病毒进入的重要受体。通路富集和 GO 分析证实了与干扰素信号和 IFN 刺激基因抗病毒机制相关的通路的富集。此外，我们还鉴定了 3 个非编码 RNA，它们可能作为与免疫机制相关基因的潜在 ceRNA。这项综合分析鉴定了非编码 RNA 及其可能的靶标，这可以有效地增强对与病毒感染相关的分子机制的理解。然而，需要进一步验证这些靶标，以确定它们的治疗效果。
