The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities
The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities
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DOI：
10.3390/v12060614
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发表时间：
2020-06-01
期刊：
影响因子：
4.7
通讯作者：
Uysal-Onganer, Pinar
中科院分区：
文献类型：
--
作者：
Arisan, Elif Damla;Dart, Alwyn;Uysal-Onganer, Pinar
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）是β冠状病毒家族的一员，可引起COVID-19疾病。SARS-CoV-2在人类中的致病性导致死亡率增加，这是由于重要途径的改变，包括一些导致与“细胞因子风暴”和广泛的肺部病理学相关的炎症反应加剧，以及与许多合并症相关。我们目前的研究比较了来自不同地理区域的5个SARS-CoV-2序列与来自SARS、MERS和两种感冒病毒OC 43和229 E的序列，以确定miR样序列的存在。我们确定了七个关键的miR，突出了SARS-CoV-2序列与其他病毒之间的显著差异。5个SARS-CoV-2序列之间的保守性水平相同，但与其他序列相比较差，SARS显示出最高的保守性。这种相似性的降低可能导致转录控制水平的降低，以及病毒的生理效应和相关宿主-病原体反应的变化。MERS和症状较轻的病毒显示出更大的差异，甚至有明显的序列缺口。这种偏离SARS-CoV-2序列的差异广泛反映了从全基因组比对中获得的系统发育关系。因此，从建立时间较长的人类病毒到较新的病毒的序列差异期间发生的突变模式可能导致了与SARS-CoV-2的致病性直接相关的序列基序的出现。重要的是，我们鉴定了7种关键microRNA（miRs 8066、5197、3611、3934- 3 p、1307- 3 p、3691- 3 p、1468- 5 p），它们与病毒致病性和宿主反应相关的KEGG途径有显著联系。根据Bioproject数据（PRJNA 615032），SARS-CoV-2介导的转录组学改变与我们研究中确定的7种miR的靶途径相似。这一机制在确定未来潜在大流行的症状谱方面可能具有相当大的意义。KEGG通路分析揭示了与7种已鉴定的miR相关的许多关键通路，这些miR可能为深入了解病毒与合并症之间的相互作用提供线索。根据我们报道的发现，miRNAs可能构成COVID-19及其病理后果的潜在和有效的治疗方法。
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of thebetacoronavirusfamily, which causes COVID-19 disease. SARS-CoV-2 pathogenicity in humans leads to increased mortality rates due to alterations of significant pathways, including some resulting in exacerbated inflammatory responses linked to the "cytokine storm" and extensive lung pathology, as well as being linked to a number of comorbidities. Our current study compared five SARS-CoV-2 sequences from different geographical regions to those from SARS, MERS and two cold viruses, OC43 and 229E, to identify the presence of miR-like sequences. We identified seven key miRs, which highlight considerable differences between the SARS-CoV-2 sequences, compared with the other viruses. The level of conservation between the five SARS-CoV-2 sequences was identical but poor compared with the other sequences, with SARS showing the highest degree of conservation. This decrease in similarity could result in reduced levels of transcriptional control, as well as a change in the physiological effect of the virus and associated host-pathogen responses. MERS and the milder symptom viruses showed greater differences and even significant sequence gaps. This divergence away from the SARS-CoV-2 sequences broadly mirrors the phylogenetic relationships obtained from the whole-genome alignments. Therefore, patterns of mutation, occurring during sequence divergence from the longer established human viruses to the more recent ones, may have led to the emergence of sequence motifs that can be related directly to the pathogenicity of SARS-CoV-2. Importantly, we identified 7 key-microRNAs (miRs 8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) with significant links to KEGG pathways linked to viral pathogenicity and host responses. According to Bioproject data (PRJNA615032), SARS-CoV-2 mediated transcriptomic alterations were similar to the target pathways of the selected 7 miRs identified in our study. This mechanism could have considerable significance in determining the symptom spectrum of future potential pandemics. KEGG pathway analysis revealed a number of critical pathways linked to the seven identified miRs that may provide insight into the interplay between the virus and comorbidities. Based on our reported findings, miRNAs may constitute potential and effective therapeutic approaches in COVID-19 and its pathological consequences.