ABSTRACT
Dengue fever is a tropical disease spread worldwide, transmitted by the mosquito Aedes aegypti. It affects 100 million people worldwide every year and half a million cases of dengue hemorrhagic fever are registered. At present, it poses sever health burden as combined infections of COVID-19. Currently, as a combined infection with COVID-19, it is becoming a serious health burden. To identify the active molecule, Maestro V12.7 was used with different tools including LigPrep, Grid Generation, SiteMap, Glide XP Docking, Pharmachophores and MM-GBSA. The UNRESS tool was also used to assess the protein stability with this dengue protein. The docking result showed that all examined phytocomponents except berberine and -(+)-l-alliin had good docking scores of -8.577 (azadirachtin), -8.112 (curcumin), -7.348 (apigenin) and -6.028 (andrographolide). However, berberine and -(+)-l-alliin possessed good hydrogen-bonding interactions with RdRp. In addition, molecular dynamic simulations demonstrate that the complex of azadirachtin and dengue protein has a solid understanding of the precise interactions. As per the research results, the present research suggests that this is the first statement of azadirachtin against NS5 RNA-dependent RNA polymerase domain (RdRp), despite extensive research on this molecule in previous investigations. Furthermore, we anticipate that molecules such as curcumin, apigenin, and andrographolide would show beneficial effects while in vitro and in vivo studies are conducted on virally related objects. Since we performed ADMET and pharmacokinetic properties in this research, we feel that the phytochemicals of the screened anti-dengue molecules may not need to be evaluated for toxicological effects.
ABSTRACT
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-ß, 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. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-022-00258-6.
ABSTRACT
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 Supplementary Information The online version contains supplementary material available at 10.1007/s43450-022-00258-6.
ABSTRACT
Dengue fever is a tropical endemic disease that is transmitted by the female Aedes aegypti mosquitoes around the world. In dengue patients, the severe vascular leak, bleeding and organ failure underlines the severity of this disease. It affects 100 million people each year and half a million cases of dengue hemorrhagic fever are recorded worldwide. In addition, the combined infections of COVID-19 and dengue fever cause serious health problems for those infected. Because polyphenolic compounds have the ability to regulate and restore the immune system, the intervention of biological tools is required to find an accurate polyphenolic compound from plants to combat these viral diseases. In this computational study, we used a range of software to explore the anti-dengue potential of the selected polyphenols, while the database was also used to explore diseased enzymes and drug targets in the dengue pathways of Homo sapiens. All examined polyphenols showed excellent docking values after molecular docking and also showed remarkable hydrogen bond interactions between the ligand and the dengue protein. Among the polyphenols tested, (R)-(+)-rosmarinic acid has a docking score of −8451 with an energy value of −59,860. After that, curcumin has the second best docking score of −8.221, followed by D - (+) - catechin (−7.042) and epicatechin (−7.069). In addition, molecular dynamic simulations demonstrate that the complex of (R) - (+) - rosmarinic acid and dengue protein has a solid understanding of the precise interactions. The current study suggests that this is the first report of such compounds against the dengue virus, despite extensive research on these substances in previous research. Moreover, we expect these polyphenols to show promising effects when used in antiviral research such as in-vitro and in-vivo studies. In addition, toxicological studies such as adsorption, distribution, metabolism, and excretion are required before further exploration of the polyphenols, as this will help to understand the biological processes of these potential polyphenols. © 2022 Elsevier Inc.