(±)-Japonones A and B, two pairs of new enantiomers with anti-KSHV activities from Hypericum japonicum

Hu, Linzhen; Zhu, Hucheng; Li, Lei; Huang, Jinfeng; Sun, Wenping; Liu, Junjun; Li, Hua; Luo, Zengwei; Wang, Jianping; Xue, Yongbo; Zhang, Yonghui

doi:10.1038/srep27588

Cited by 22 publications

(12 citation statements)

References 31 publications

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“…The 3D-formatted molecule was imported into the Pharmaceutical Target Seeker (PTS; http://www.rcdd.org.cn/PTS/result ), and a search was conducted. Molecular modeling was conducted with the SYBYL program package ( 20 ). Eleutheroside B1 was used as the template.…”

Section: Methodsmentioning

confidence: 99%

Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation

Wen

Zheng

et al. 2018

Int J Mol Med

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Influenza viruses represent a serious threat to human health. Although our research group has previously demonstrated the antiviral and anti-inflammatory activities of eleutheroside B1, a detailed explanation of the mechanism by which it is effective against the influenza virus remains to be elucidated. In the present study, the transcriptomic responses of influenza A virus-infected lung epithelial cells (A549) treated with eleutheroside B1 were investigated using high-throughput RNA sequencing, and potential targets were identified using a molecular docking technique, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay, and DNA methylation analysis. The transcriptomic data revealed that there are 1,871 differentially expressed genes (DEGs) between the cells infected with the influenza virus strain variant PR8, and the cells infected with PR8 and treated with eleutheroside B1. Among the DEGs, RNA polymerase II subunit A (POLR2A; encoding the largest subunit of RNA polymerase II) and mannosidase α class II member 1 (MAN2A1) were selected from the molecular docking analysis with eleutheroside B1. The docking score of Drosophila melanogaster MAN2A1 (3BVT) was 11.3029, whereas that of POLR2A was 9.0133. The RT-qPCR results demonstrated that the expression levels of host genes (MAN2A2, POLR2A) and viral genes (PA, PB1, PB2, HA) were downregulated following eleutheroside B1 treatment. Bisulfite-sequencing PCR was performed to investigate whether eleutheroside B1 was able to modify the DNA methylation of POLR2A, and the results suggested that the average proportion of methylated CpGs (-222-72 bp) increased significantly following treatment with eleutheroside B1. Taken together, these findings suggested that eleutheroside B1 may affect N-glycan biosynthesis, the chemokine signaling pathway, cytokine-cytokine receptor interaction and, in particular, may target the POLR2A to inhibit the production of influenza virus genes.

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Section: Methodsmentioning

confidence: 99%

Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation

Wen

Zheng

et al. 2018

Int J Mol Med

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“…The IC 50 values of ( 45) and (46) were 8.30 and 4.90 µM, the SI values were 23.49 and 25.70, respectively. (+)-japonone A (47) exhibited inhibitory activity with an IC 50 of 166.0 µM, CC 50 > 500 µM, and SI > 3.01 on KSHV lytic replication with less toxicity and better selectivity than (−)-japonone A with inert activities on anti-KSHV [146]. Japopyrone B (48) exhibited potential inhibitory efficacy on TPA-induced KSHV lytic replication with an IC 50 of 29.46 µM, CC 50 > 200, and SI > 6.79 [147].…”

Section: Miscellaneous Compounds With Potential Antiherpetic Activitiesmentioning

confidence: 99%

Natural Products and Their Derivatives against Human Herpesvirus Infection

et al. 2021

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Herpesviruses establish long-term latent infection for the life of the host and are known to cause numerous diseases. The prevalence of viral infection is significantly increased and causes a worldwide challenge in terms of health issues due to drug resistance. Prolonged treatment with conventional antiviral drugs is more likely to develop drug-resistant strains due to mutations of thymidine nucleoside kinase or DNA polymerase. Hence, the development of alternative treatments is clearly required. Natural products and their derivatives have played a significant role in treating herpesvirus infection rather than nucleoside analogs in drug-resistant strains with minimal undesirable effects and different mechanisms of action. Numerous plants, animals, fungi, and bacteria-derived compounds have been proved to be efficient and safe for treating human herpesvirus infection. This review covers the natural antiherpetic agents with the chemical structural class of alkaloids, flavonoids, terpenoids, polyphenols, anthraquinones, anthracyclines, and miscellaneous compounds, and their antiviral mechanisms have been summarized. This review would be helpful to get a better grasp of anti-herpesvirus activity of natural products and their derivatives, and to evaluate the feasibility of natural compounds as an alternative therapy against herpesvirus infections in humans.

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“…The compounds were saved as mol2 files and used as an input for docking. The docking was performed using the Surflx-Dock module of the Sybyl softare 28 , 29 . Ligand binding pocket residues were selected using graphical tools in the Sybyl software to create the boundaries of the docking search.…”

Section: Biological Activities Evaluationmentioning

confidence: 99%

“…All of the hydrogen atoms were added to define the correct ionization and tautomeric states, and the carboxylate, phosphonate and sulphonate groups were considered in their charged form. In the docking calculation, the default FlexX scoring function was used for exhaustive searching, solid body optimizing and interaction scoring 28 , 29 . The pose with the lowest-energy and the most favorable score was remained.…”

Section: Biological Activities Evaluationmentioning

confidence: 99%

Aspermerodione, a novel fungal metabolite with an unusual 2,6-dioxabicyclo[2.2.1]heptane skeleton, as an inhibitor of penicillin-binding protein 2a

Qiao

Zhang

et al. 2018

Sci Rep

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Rising drug resistance limits the treatment options infected by methicillin-resistant Staphylococcus aureus (MRSA). A promising solution for overcoming the resistance of MRSA is to inhibit the penicillin-binding protein 2a (PBP2a). A novel terpene-polyketide hybrid meroterpenoid, aspermerodione (1), characterized by an unusual 2,6-dioxabicyclo[2.2.1]heptane core skeleton, and a new heptacyclic analogue, andiconin C (2), were isolated and identified from the liquid cultures of endophytic fungus Aspergillus sp. TJ23. The structures and their absolute configurations of all chiral centers were elucidated via extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations and determined via single-crystal X-ray diffraction analysis. Aspemerodione (1) was found to be a potential inhibitor of PBP2a, and work synergistically with the β-lactam antibiotics oxacillin and piperacillin against MRSA.

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(±)-Japonones A and B, two pairs of new enantiomers with anti-KSHV activities from Hypericum japonicum

Cited by 22 publications

References 31 publications

Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation

Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation

Natural Products and Their Derivatives against Human Herpesvirus Infection

Aspermerodione, a novel fungal metabolite with an unusual 2,6-dioxabicyclo[2.2.1]heptane skeleton, as an inhibitor of penicillin-binding protein 2a

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