Computational Analysis of Targeting SARS-CoV-2, Viral Entry Proteins ACE2 and TMPRSS2, and Interferon Genes by Host MicroRNAs.
Computational Analysis of Targeting SARS-CoV-2, Viral Entry Proteins ACE2 and TMPRSS2, and Interferon Genes by Host MicroRNAs.
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通过宿主microRNA靶向SARS-CoV-2、病毒进入蛋白ACE 2和TMPRSS 2以及干扰素基因的计算分析。
DOI：
10.3390/genes11111354
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发表时间：
2020-11-16
期刊：
影响因子：
3.5
通讯作者：
Feinberg MW
中科院分区：
文献类型：
--
作者：
Pierce JB;Simion V;Icli B;Pérez-Cremades D;Cheng HS;Feinberg MW
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)是导致2019年冠状病毒病(新冠肺炎)的病毒，其迅速传播已导致全球大流行、当地医疗保健系统故障和全球经济衰退。近年来，microRNAs(MiRNAs)已成为病毒致病的重要调节因子，尤其是在RNA病毒中，但宿主miRNAs对SARS-CoV-2感染性的影响尚不清楚。在这项研究中，我们利用强大的生物信息学预测算法和miRNA图谱相结合的方法来预测内源性宿主miRNAs，这些miRNAs可能在调节SARS-CoV-2感染性方面发挥重要作用。我们提供了SARS-CoV-2基因组以及关键病毒进入蛋白ACE2和TMPRSS2及其上游调节因子干扰素(干扰素)的高概率miRNA结合位点的集合。通过利用SARS-CoV-2抗性和易感细胞系的miRNA图谱数据集，我们验证了预测的miRNA与靶RNA相互作用的生物学合理性。最后，我们利用SARS-CoV-2感染细胞的miRNA图谱来识别在感染细胞中差异调控的预测miRNAs。特别是，我们鉴定了预测的SARS-CoV-2 ORF的miRNA结合子(miR-23a(1AB)，miR-29a，-29c(1AB，N)，miR-151a，-151b(S)，miR-4707-3p(S)，miR-298(5‘-Utr)，miR-7851-3p(5’-Utr)，miR-8075(5‘-Utr)，ACE23’-Utr(miR-9-5p，miR-218-5p)，TMPRSS23‘-Utr(let-7d-5p，-7e-5p，miR-494-3p，MiR-382-3p、miR-181c-5p)和干扰素-α3‘-UtR(miR-361-5p、miR-410-3p)。综上所述，本研究提供了宿主miRNAs对SARS-CoV-2潜在的新的调控机制，并为未来将这些miRNAs作为潜在的治疗靶点或生物标志物的研究奠定了基础。
Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has led to a global pandemic, failures of local health care systems, and global economic recession. MicroRNAs (miRNAs) have recently emerged as important regulators of viral pathogenesis, particularly among RNA viruses, but the impact of host miRNAs on SARS-CoV-2 infectivity remains unknown. In this study, we utilize the combination of powerful bioinformatic prediction algorithms and miRNA profiling to predict endogenous host miRNAs that may play important roles in regulating SARS-CoV-2 infectivity. We provide a collection of high-probability miRNA binding sites within the SARS-CoV-2 genome as well as within mRNA transcripts of critical viral entry proteins ACE2 and TMPRSS2 and their upstream modulators, the interferons (IFN). By utilizing miRNA profiling datasets of SARS-CoV-2-resistant and -susceptible cell lines, we verify the biological plausibility of the predicted miRNA–target RNA interactions. Finally, we utilize miRNA profiling of SARS-CoV-2-infected cells to identify predicted miRNAs that are differentially regulated in infected cells. In particular, we identify predicted miRNA binders to SARS-CoV-2 ORFs (miR-23a (1ab), miR-29a, -29c (1ab, N), miR-151a, -151b (S), miR-4707-3p (S), miR-298 (5′-UTR), miR-7851-3p (5′-UTR), miR-8075 (5′-UTR)), ACE2 3′-UTR (miR-9-5p, miR-218-5p), TMPRSS2 3′-UTR (let-7d-5p, -7e-5p, miR-494-3p, miR-382-3p, miR-181c-5p), and IFN-α 3′-UTR (miR-361-5p, miR-410-3p). Overall, this study provides insight into potential novel regulatory mechanisms of SARS-CoV-2 by host miRNAs and lays the foundation for future investigation of these miRNAs as potential therapeutic targets or biomarkers.
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