Absorbed plant MIR2911 in honeysuckle decoction inhibits SARS-CoV-2 replication and accelerates the negative conversion of infected patients.
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ABSTRACT:
SUBMITTER: Zhou LK
PROVIDER: S-EPMC7406496 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Absorbed plant MIR2911 in honeysuckle decoction inhibits SARS-CoV-2 replication and accelerates the negative conversion of infected patients.
Zhou Li-Kun LK Zhou Zhen Z Jiang Xia-Ming XM Zheng Yishan Y Chen Xi X Fu Zheng Z Xiao Gengfu G Zhang Chen-Yu CY Zhang Lei-Ke LK Yi Yongxiang Y
Cell discovery 20200805 1
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Project description:The highly abundant and stable antiviral small RNA derived from honeysuckle, known as miR2911, has been shown to play a key role in inhibiting influenza virus infection and SARS-CoV-2 infection. However, whether miR2911 inhibits the replication of porcine reproductive and respiratory syndrome virus (PRRSV) remains unknown. Hence, this study investigated the mechanisms underlying the action of miR2911 during PRRSV infection. Six targets of miR2911 within the PRRSV orf1 (Nsp2: 2459 to 2477, 1871 to 1892, 954 to 977, and 1271 to 1292; Nsp1: 274 to 296 and 822 to 841) were successfully identified by using the miRanda v1.0b software. The miR2911 target sequence was analyzed by target sequence comparison, and only individual base mutations existed in different prevalent strains, and the miR2911 target region was highly conserved among different strains. Subsequently, through the dual luciferase reporter gene assay and miR2911 overexpression assay, it was demonstrated that miR2911 significantly inhibits the replication of PRRSV by targeting regions of PRRSV Nsp1 and Nsp2. These findings offer new insights for the development of novel anti-PRRSV drugs.
| S-EPMC11435848 | biostudies-literature
Project description:Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and improved viral infection-induced mouse weight loss but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction both dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection.
2014-10-22 | GSE55268 | GEO
Project description:Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and improved viral infection-induced mouse weight loss but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction both dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection. Screening and profiling of known plant microRNA in HS and HS decoction
2014-10-22 | E-GEOD-55268 | biostudies-arrayexpress
Project description:Dengue virus (DENV) infection causes mild to severe illness in humans that can lead to fatality in severe cases. Currently, no specific drug is available for the treatment of DENV infection. Thus, the development of an anti-DENV drug is urgently required. Cordycepin (3'-deoxyadenosine), which is a major bioactive compound in Cordyceps (ascomycete) fungus that has been used for centuries in Chinese traditional medicine, was reported to exhibit antiviral activity. However, the anti-DENV activity of cordycepin is unknown. We hypothesized that cordycepin exerts anti-DENV activity and that, as an adenosine derivative, it inhibits DENV replication. To test this hypothesis, we investigated the anti-DENV activity of cordycepin in DENV-infected Vero cells. Cordycepin treatment significantly decreased DENV protein at a half-maximal effective concentration (EC50) of 26.94 μM. Moreover, DENV RNA was dramatically decreased in cordycepin-treated Vero cells, indicating its effectiveness in inhibiting viral RNA replication. Via in silico molecular docking, the binding of cordycepin to DENV non-structural protein 5 (NS5), which is an important enzyme for RNA synthesis, at both the methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, was predicted. The results of this study demonstrate that cordycepin is able to inhibit DENV replication, which portends its potential as an anti-dengue therapy.
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Project description:BackgroundHoneysuckle is a time-honored herb with anticancer activity in traditional Chinese medicine. Recently, accumulating reports are suggesting that the microRNAs in this medicinal plant not only play a physiological role in their original system, but also can be transmitted to another species as potential therapeutic components. In the numerous bioactive investigations, the anti-tumor effects of these microRNAs in the magical herb are rarely studied, especially the special miR2911, a honeysuckle-encoded atypical microRNA, with high stability during the boiling process and unique biological activity to target TGF-β1 mRNA.MethodsLuciferase assay was conducted to test the ability of miR2911 to target TGF-β1 mRNA. ELISA was performed to determine the expression level of TGF-β1 of mouse colorectal adenocarcinoma CT26 cells when treated with miR2911 and tumor tissue in Sidt1+/+ and Sidt1-/- mice. qRT-PCR was performed to examine the level of expression of miR2911. Tumor-bearing wild and nude mice were employed to evaluate the anti-tumor effect of honeysuckle and miR2911 in vivo. Tumor tissue necrosis was observed by H&E staining. Besides, the infiltration of T lymphocytes across solid tumors was tested by immunostaining staining.ResultsOur results showed that honeysuckle slowed the development of colon cancer down. Further research showed that miR2911 could bind strongly to TGF-β1 mRNA and down-regulate the expression of TGF-β1 and had a high stability under boiling and acid condition. Moreover, SIDT1 mediated dietary miR2911 inter-species absorption. And we found that miR2911 had a similar anticancer effect as honeysuckle. Mechanistically, miR2911 reversed the tumor-promoting effect of TGF-β1 by an increase of T lymphocytes infiltration, resulting in slowing the colon cancer process in immunocompetent mice. Consistent with this inference, the anti-tumor effect of miR2911 was revealed to be abolished in T cell immune deficiency mice.ConclusionTaken together, honeysuckle-derived miR2911 showed an anti-tumor effect in colon cancer through targeting TGF-β1 mRNA. The down-regulation of TGF-β1 promoted T lymphocytes infiltration, and accordingly impeded the colon tumor development.
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Project description:Melamine-derived mesoporous carbon, which was obtained from pyrolysis of modified melamine, was employed for the purpose of eliminating trace amounts of Hg(II) from honeysuckle decoction. The specific surface area of the mesoporous carbons with N-functional (MCN1) was 648.372 m2·g-1. The chemical composition and morphology of MCN1 were thoroughly examined, and a comprehensive analysis led to the identification of its formation mechanism. A noteworthy association has been identified between the adsorption efficacy and the chemical composition of MCN1. In the elimination of trace mercury in aqueous solutions over a broad pH range (pH 2-9), MCN1 demonstrates high effectiveness, approaching 100%. Adsorption kinetics and isotherm results indicate that a more accurate representation of Hg(II) adsorption on MCN1 is provided by pseudo-second-order kinetics and Freundlich models, with chemical adsorption being the dominant mechanism. This study further examined the removal of chlorogenic acid, a bioactive component, by MCN1. The findings imply that MCN1 has a noteworthy 80% efficacy in removing mercury from honeysuckle decoction while maintaining the purity of its medicinal ingredients, particularly chlorogenic acid. As a result, utilizing MCN1 for the adsorption of Hg(II) in honeysuckle decoction appears to be a reasonable approach.
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