In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection.
In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection.
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DOI：
10.1038/s41598-021-89605-6
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发表时间：
2021-05-13
影响因子：
4.6
通讯作者：
Moradi S
中科院分区：
文献类型：
--
作者：
Ahmadi A;Moradi S
当前，新冠肺炎疫情已成为世界面临的最大挑战。目前还没有针对COVID-19的特异性药物，这为确定新的候选药物留下了关键空白。最近的研究报道了小分子依诺沙星通过增强RNAi途径发挥抗病毒活性。本研究的目的是分析依诺沙星是否能发挥抗sars - cov -2的作用。我们利用多种计算工具和数据库来研究(i)作为依诺沙星靶通路的RNAi机制是否可以作用于SARS-CoV-2基因组，以及（ii）依诺沙星诱导的microrna是否可以直接沉默病毒成分以及介导病毒进入和复制的宿主细胞蛋白。我们发现SARS-CoV-2的RNA基因组可能是DICER活性的合适底物。我们还强调了几种依诺沙星增强的microrna，它们可以靶向SARS-CoV-2成分、促炎细胞因子、促进病毒复制的宿主细胞成分和肺干细胞中富集的转录因子，从而促进其分化和肺再生。最后，我们的分析确定了几个以依诺沙星为目标的调节模块，这些模块与SARS-CoV-2感染的恶化有关键关系。总的来说，我们的分析表明，依诺沙星可能是通过增强RNAi途径治疗COVID-19的有希望的候选者。
COVID-19 has currently become the biggest challenge in the world. There is still no specific medicine for COVID-19, which leaves a critical gap for the identification of new drug candidates for the disease. Recent studies have reported that the small-molecule enoxacin exerts an antiviral activity by enhancing the RNAi pathway. The aim of this study is to analyze if enoxacin can exert anti-SARS-CoV-2 effects. We exploit multiple computational tools and databases to examine (i) whether the RNAi mechanism, as the target pathway of enoxacin, could act on the SARS-CoV-2 genome, and (ii) microRNAs induced by enoxacin might directly silence viral components as well as the host cell proteins mediating the viral entry and replication. We find that the RNA genome of SARS-CoV-2 might be a suitable substrate for DICER activity. We also highlight several enoxacin-enhanced microRNAs which could target SARS-CoV-2 components, pro-inflammatory cytokines, host cell components facilitating viral replication, and transcription factors enriched in lung stem cells, thereby promoting their differentiation and lung regeneration. Finally, our analyses identify several enoxacin-targeted regulatory modules that were critically associated with exacerbation of the SARS-CoV-2 infection. Overall, our analysis suggests that enoxacin could be a promising candidate for COVID-19 treatment through enhancing the RNAi pathway.
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影响因子：
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