Dataset Information

Dibromopinocembrin and Dibromopinostrobin Are Potential Anti-Dengue Leads with Mild Animal Toxicity.

ABSTRACT: Dengue infection is one of the most deleterious public health concerns for two-billion world population being at risk. Plasma leakage, hemorrhage, and shock in severe cases were caused by immunological derangement from secondary heterotypic infection. Flavanone, commonly found in medicinal plants, previously showed potential as anti-dengue inhibitors for its direct antiviral effects and suppressing the pro-inflammatory cytokine from dengue immunopathogenesis. Here, we chemically modified flavanones, pinocembrin and pinostrobin, by halogenation and characterized them as potential dengue 2 inhibitors and performed toxicity tests in human-derived cells and in vivo animal model. Dibromopinocembrin and dibromopinostrobin inhibited dengue serotype 2 at the EC50s of 2.0640 ± 0.7537 and 5.8567 ± 0.5074 µM with at the CC50s of 67.2082 ± 0.9731 and >100 µM, respectively. Both of the compounds also showed minimal toxicity against adult C57BL/6 mice assessed by ALT and Cr levels in day one, three, and eight post-intravenous administration. Computational studies suggested the potential target be likely the NS5 methyltransferase at SAM-binding pocket. Taken together, these two brominated flavanones are potential leads for further drug discovery investigation.

SUBMITTER: Boonyasuppayakorn S

PROVIDER: S-EPMC7571160 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Dibromopinocembrin and Dibromopinostrobin Are Potential Anti-Dengue Leads with Mild Animal Toxicity.

Boonyasuppayakorn Siwaporn S Saelee Thanaphon T Visitchanakun Peerapat P Leelahavanichkul Asada A Hengphasatporn Kowit K Shigeta Yasuteru Y Huynh Thao Nguyen Thanh TNT Chu Justin Jang Hann JJH Rungrotmongkol Thanyada T Chavasiri Warinthorn W

Molecules (Basel, Switzerland) 20200911 18

Dengue infection is one of the most deleterious public health concerns for two-billion world population being at risk. Plasma leakage, hemorrhage, and shock in severe cases were caused by immunological derangement from secondary heterotypic infection. Flavanone, commonly found in medicinal plants, previously showed potential as anti-dengue inhibitors for its direct antiviral effects and suppressing the pro-inflammatory cytokine from dengue immunopathogenesis. Here, we chemically modified flavano ...[more]

PMID: 32932762

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Project description:Dengue fever has become one of the deadliest infectious diseases and requires the development of effective antiviral therapies. It is caused by members of the Flaviviridae family, which also cause various infections in humans, including dengue fever, tick-borne encephalitis, West Nile fever, and yellow fever. In addition, since 2019, dengue-endemic regions have been grappling with the public health and socio-economic impact of the ongoing coronavirus disease 19. Co-infections of coronavirus and dengue fever cause serious health complications for people who also have difficulty managing them. To identify the potentials of mangiferin, a molecular docking with various dengue virus proteins was performed. In addition, to understand the gene interactions between human and dengue genes, Cytoscape was used in this research. The Kyoto Encyclopedia of Genes and Genomes software was used to find the paths of Flaviviridae. The Kyoto Encyclopedia of Genes and Genomes and the Reactome Pathway Library were used to understand the biochemical processes involved. The present results show that mangiferin shows efficient docking scores and that it has good binding affinities with all docked proteins. The exact biological functions of type I interferon, such as interferon-α and interferon-β, were also shown in detail through the enrichment analysis of the signaling pathway. According to the docking results, it was concluded that mangiferin could be an effective drug against the complications of dengue virus 1, dengue virus 3, and non-structural protein 5. In addition, computational biological studies lead to the discovery of a new antiviral bioactive molecule and also to a deeper understanding of viral replication in the human body. Ultimately, the current research will be an important resource for those looking to use mangiferin as an anti-dengue drug.Graphical abstractSupplementary informationThe online version contains supplementary material available at 10.1007/s43450-022-00258-6.

Dataset Information

Dibromopinocembrin and Dibromopinostrobin Are Potential Anti-Dengue Leads with Mild Animal Toxicity.

Publications

Dibromopinocembrin and Dibromopinostrobin Are Potential Anti-Dengue Leads with Mild Animal Toxicity.

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