Flavivirus Entry Inhibitors

Wang, Qing Yin; Shi, Pei–Yong

doi:10.1021/acsinfecdis.5b00066

Cited by 28 publications

(19 citation statements)

References 76 publications

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“…More importantly, these inhibitors can exert their effect through direct binding to virions without the need to cross the hydrophobic membrane bilayer and be delivered into infected cells. However, due to the complexity and high variability of flaviviral E protein, it is challenging to develop pan-serotype inhibitors (Wang and Shi, 2015 ).…”

Section: Targeting Ld Metabolism As Antiviral Strategiesmentioning

confidence: 99%

Modulation of Lipid Droplet Metabolism—A Potential Target for Therapeutic Intervention in Flaviviridae Infections

2017

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Lipid droplets (LDs) are endoplasmic reticulum (ER)-related dynamic organelles that store and regulate fatty acids and neutral lipids. They play a central role in cellular energy storage, lipid metabolism and cellular homeostasis. It has become evident that viruses have co-evolved in order to exploit host lipid metabolic pathways. This is especially characteristic of the Flaviviridae family, including hepatitis C virus (HCV) and several flaviviruses. Devoid of an appropriate lipid biosynthetic machinery of their own, these single-strand positive-sense RNA viruses can induce dramatic changes in host metabolic pathways to establish a favorable environment for viral multiplication and acquire essential components to facilitate their assembly and traffic. Here we have reviewed the current knowledge on the intracellular life cycle of those from the Flaviviridae family, with particular emphasis on HCV and dengue virus (DENV), and their association with the biosynthesis and metabolism of LDs, with the aim to identify potential antiviral targets for development of novel therapeutic interventions.

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Section: Targeting Ld Metabolism As Antiviral Strategiesmentioning

confidence: 99%

Modulation of Lipid Droplet Metabolism—A Potential Target for Therapeutic Intervention in Flaviviridae Infections

2017

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“…Therefore, it is of utmost urgency to develop safe and effective anti-ZIKV compounds, not only to mitigate ZIKV-associated morbidities but also to impair the chain of transmission. The features of E mediated events make the development of entry inhibitors an attractive possibility 10 . Medicinal plants, which have been used as treatment or prevention against human diseases for millenaries, remain a remarkable source of potential antiviral compounds.…”

Section: Introductionmentioning

confidence: 99%

Extract from Aphloia theiformis, an edible indigenous plant from Reunion Island, impairs Zika virus attachment to the host cell surface

Clain

Sinigaglia

Koishi

et al. 2018

Sci Rep

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The mosquito-borne Zika virus (ZIKV) belongs to the flavivirus genus of the Flaviviridae family. Contemporary epidemic strains of ZIKV are associated with congenital malformations in infants, including microcephaly, as well as Guillain-Barré syndrome in adults. A risk of human-to-human transmission of ZIKV is also well documented. A worldwide research effort has been undertaken to identify safe and effective strategies to prevent or treat ZIKV infection. We show here that extract from Aphloia theiformis, an edible endemic plant from Indian Ocean islands, exerts a potent antiviral effect against ZIKV strains of African and Asian lineages, including epidemic strains. The antiviral effect of A. theiformis extract was extended to clinical isolates of dengue virus (DENV) of the four serotypes in human hepatocytes. A. theiformis inhibited virus entry in host cells by acting directly on viral particles, thus impairing their attachment to the cell surface. Electron microscopic observations revealed that organization of ZIKV particles was severely affected by A. theiformis. We propose a model of antiviral action for A. theiformis against flaviviruses that highlights the potential of medicinal plants as promising sources of naturally-derived antiviral compounds to prevent ZIKV and DENV infections.

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“…Our results indicate that Carrageenan inhibits JEV mainly through its direct virucidal effects and interference within the early stages of viral infection, such as viral attachment and cellular entry. We postulated that the direct antiviral activity of Carrageenan might be due to their ability to interact with the virus envelop glycoprotein, particularly the flavivirus E protein, which is responsible for JEV adsorption through the host membrane [18, 19]. Besides, Carrageenan also showed a significant inhibitory effect in the viral attachment assay.…”

Section: Discussionmentioning

confidence: 99%

Antiviral and Virucidal activities of sulphated polysaccharides against Japanese Encephalitis Virus

Rothan

Yusof

2020

Preprint

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BackgroundJapanese encephalitis virus (JEV), a member of the family Flaviviridae, causes severe neurological disorders in humans. JEV infections represent one of the most widely spread mosquito-borne diseases, and therefore, it has been considered as an endemic disease. An effective antiviral drug is still unavailable to treat JEV, and current drugs only provide supportive treatment to alleviate the symptoms and stabilize patients’ conditions. This study was designed to evaluate the antiviral activity of the sulphated polysaccharides “Carrageenan,” a linear sulphated polysaccharide that is extracted from red edible seaweeds against JEV replication in vitro.Methods and ResultsViral inactivation, attachment, and post-infection assays were used to determine the mode of inhibition of Carrageenan. Virus titters after each application were evaluated by plaque formation assay. MTT assay was used to determine the 50% cytotoxic concentration (CC50), and ELISA-like cell-based assay and immunostaining and immunostaining techniques were used to evaluate the 50% effective concentration (EC50). This study showed that Carrageenan inhibited JEV at an EC50 of 15 μg/mL in a dose-dependent manner with CC50 more than 200 μg/mL in healthy human liver cells (WRL68). The mode of inhibition assay showed that the antiviral effects of Carrageenan are mainly due to their ability to inhibit the early stages of virus infection such as the viral attachment and the cellular entry stages.ConclusionOur investigation showed that Carrageenan could be considered as a potent antiviral agent to JEV infection. Further experimental and clinical studies are needed to investigate the potential applications of Carrageenan for clinical intervention against JEV infection.

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Flavivirus Entry Inhibitors

Cited by 28 publications

References 76 publications

Modulation of Lipid Droplet Metabolism—A Potential Target for Therapeutic Intervention in Flaviviridae Infections

Modulation of Lipid Droplet Metabolism—A Potential Target for Therapeutic Intervention in Flaviviridae Infections

Extract from Aphloia theiformis, an edible indigenous plant from Reunion Island, impairs Zika virus attachment to the host cell surface

Antiviral and Virucidal activities of sulphated polysaccharides against Japanese Encephalitis Virus

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