Natarelli Lucia, Parca Luca, Mazza Tommaso, Weber Christian, Virgili Fabio, Fratantonio Deborah
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universität (LMU), 800336 Munich, Germany.
IRCCS Casa sollievo della Sofferenza, Laboratory of Bioinformatics, 71013 San Giovanni Rotondo (FG), Italy.
Noncoding RNA. 2021 Feb 18;7(1):14. doi: 10.3390/ncrna7010014.
The respiratory system is one of the most affected targets of SARS-CoV-2. Various therapies have been utilized to counter viral-induced inflammatory complications, with diverse success rates. Pending the distribution of an effective vaccine to the whole population and the achievement of "herd immunity", the discovery of novel specific therapies is to be considered a very important objective. Here, we report a computational study demonstrating the existence of target motifs in the SARS-CoV-2 genome suitable for specific binding with endogenous human micro and long non-coding RNAs (miRNAs and lncRNAs, respectively), which can, therefore, be considered a conceptual background for the development of miRNA-based drugs against COVID-19. The SARS-CoV-2 genome contains three motifs in the 5'UTR leader sequence recognized by selective nucleotides within the seed sequence of specific human miRNAs. The seed of 57 microRNAs contained a "GGG" motif that promoted leader sequence-recognition, primarily through offset-6mer sites able to promote microRNAs noncanonical binding to viral RNA. Similarly, lncRNA H19 binds to the 5'UTR of the viral genome and, more specifically, to the transcript of the viral gene Spike, which has a pivotal role in viral infection. Notably, some of the non-coding RNAs identified in our study as candidates for inhibiting SARS-CoV-2 gene expression have already been proposed against diverse viral infections, pulmonary arterial hypertension, and related diseases.
呼吸系统是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）最易感染的靶标之一。人们已采用多种疗法来对抗病毒引发的炎症并发症，成功率各不相同。在向全体人群分发有效疫苗并实现“群体免疫”之前，发现新的特异性疗法应被视为一个非常重要的目标。在此，我们报告一项计算研究，该研究证明了SARS-CoV-2基因组中存在适合与内源性人类微小RNA和长链非编码RNA（分别为miRNA和lncRNA）特异性结合的靶基序，因此，这可被视为开发抗COVID-19的基于miRNA的药物的概念背景。SARS-CoV-2基因组在5'UTR前导序列中包含三个基序，这些基序可被特定人类miRNA种子序列中的选择性核苷酸识别。57种微小RNA的种子包含一个“GGG”基序，该基序主要通过能够促进微小RNA与病毒RNA非经典结合的偏移6聚体位点来促进前导序列识别。同样，lncRNA H19与病毒基因组的5'UTR结合，更具体地说，与病毒基因刺突（Spike）的转录本结合，刺突在病毒感染中起关键作用。值得注意的是，我们研究中确定的一些作为抑制SARS-CoV-2基因表达候选物的非编码RNA，已被提议用于对抗多种病毒感染、肺动脉高压及相关疾病。
