Edible plant-derived exosomal microRNAs: Exploiting a cross-kingdom regulatory mechanism for targeting SARS-CoV-2.

Edible plant-derived exosomal microRNAs: Exploiting a cross-kingdom regulatory mechanism for targeting SARS-CoV-2.
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DOI:
10.1016/j.taap.2021.115425
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发表时间:
2021-03-01
影响因子:
3.8
通讯作者:
Sundaram GM
Sundaram GM
中科院分区:
医学3区
文献类型:
--
作者:
Kalarikkal SP;Sundaram GM

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当前的COVID-19大流行是由冠状病毒科的SARS-CoV-2引起的。尽管全球流行,但目前没有疫苗或药物。膳食来源的植物外泌体样囊泡被称为可食用纳米颗粒(ENPs)。ENPs以生物可利用的形式充满了microrna (mirna)。最近,植物mirna对人类转录物的跨界调控已经得到证实。然而,ENP衍生的靶向SARS-CoV-2的mirna尚未被描述。成熟的enp衍生的miRNA序列从文献中可用的小RNA测序数据集中检索。进行了计算机靶标预测,以鉴定可能靶向SARS-CoV-2的mirna。从生姜和柚子植物中分离到ENPs,并通过qRT-PCR证实了SARS-CoV-2靶向mirna的表达。从总共260个enp衍生的mirna中,我们鉴定出22个可能潜在靶向SARS-CoV-2基因组的mirna。11种miRNAs对SARS-CoV-2表现出绝对的靶向特异性,但对SARS-CoV没有特异性。来自大豆、生姜、哈密瓜、葡萄柚、番茄和梨的ENPs具有针对SARS-CoV-2不同区域的多个mirna。有趣的是,osa/cme miR-530b-5p特异性靶向ORF1a和ORF1b之间的核糖体滑移位点。我们通过RT-PCR验证了6种mirna (miR-5077、miR-6300、miR-156a、miR-169、miR-5059和miR-166 m)在生姜和柚子ENPs中的相对表达,结果显示生姜和柚子ENPs中特异性mirna的富集存在差异。由于给药ENPs会导致其在体内积聚到肺组织中,因此ENP衍生的靶向SARS-CoV-2基因组的mirna有可能被开发为一种替代疗法。
The current COVID-19 pandemic is caused by SARS-CoV-2 which belongs to coronaviridae family. Despite the global prevalence, there are currently no vaccines or drugs. Dietary plant derived exosome-like vesicles are known as edible nanoparticles (ENPs). ENPs are filled with microRNAs (miRNAs), in bioavailable form. Recently, cross-kingdom regulation of human transcripts by plant miRNAs have been demonstrated. However, ENP derived miRNAs targeting SARS-CoV-2 has not been described. Mature ENP-derived miRNA sequences were retrieved from small RNA sequencing datasets available in the literature. In silico target prediction was performed to identify miRNAs that could target SARS-CoV-2. ENPs were isolated from ginger and grapefruit plants and the expression of SARS-CoV-2 targeting miRNAs were confirmed by qRT-PCR. From a total of 260 ENP-derived miRNAs, we identified 22 miRNAs that could potentially target SARS-CoV-2 genome. 11 miRNAs showed absolute target specificity towards SARS-CoV-2 but not SARS-CoV. ENPs from soybean, ginger, hamimelon, grapefruit, tomato and pear possess multiple miRNAs targeting different regions within SARS-CoV-2. Interestingly, osa/cme miR-530b-5p specifically targeted the ribosomal slippage site between ORF1a and ORF1b. We validated the relative expression of six miRNAs (miR-5077, miR-6300, miR-156a, miR-169, miR-5059 and miR-166 m) in ginger and grapefruit ENPs by RT-PCR which showed differential enrichment of specific miRNAs in ginger and grapefruit ENPs. Since administration of ENPs leads to their accumulation into lung tissues in vivo, ENP derived miRNAs targeting SARS-CoV-2 genome has the potential to be developed as an alternative therapy.
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