Dengue fever is one of the most important mosquito-borne viral infections in large parts of tropical and subtropical countries and is a significant public health concern and socioeconomic burden. There is an urgent need to develop antivirals that can effectively reduce dengue virus (DENV) replication and decrease viral load. Niclosamide, an antiparasitic drug approved for human use, has been recently identified as an effective antiviral agent against a number of pH-dependent viruses, including flaviviruses. Here, we reveal that neutralization of low-pH intracellular compartments by niclosamide affects multiple steps of the DENV infectious cycle. Specifically, niclosamide-induced endosomal neutralization not only prevents viral RNA replication but also affects the maturation of DENV particles, rendering them non-infectious. We found that niclosamide-induced endosomal neutralization prevented E glycoprotein conformational changes on the virion surface of flaviviruses, resulting in the release of non-infectious immature virus particles with uncleaved pr peptide from host cells. Collectively, our findings support the potential application of niclosamide as an antiviral agent against flavivirus infection and highlight a previously uncharacterized mechanism of action of the drug.
Aim: Prussian blue nanoparticles (PB NPs) have been reported as excellent antioxidant agents owing to their ability to scavenge reactive oxygen species. However, their poor stability in vivo limits their use in biomedical applications. Materials & methods: In this study, we developed chitosan-templated PB NPs using water-soluble chitosan samples with molecular weights ranging from 3 to 100 kDa, which stabilized the PB NPs and improved their antioxidant activity. Results & conclusion: The chitosan-templated PB NPs coordinated with the optimal chitosan molecular weight had uniform sphere-like particles, improved stability and effective scavenging activity of in vitro reactive oxygen species generation in murine fibroblast cells stimulated by oxidative stress agents without any cytotoxicity, implying that they could be promising antioxidant agents.
Background: Astaxanthin (ASTA), a carotenoid, is a strong antioxidant. However, its application in functional foods, pharmaceuticals, and cosmetics remains limited due to its low aqueous solubility and stability. Several different encapsulating materials have been used to improve the stability and bioavailability of ASTA; however, the currently investigated nano-carriers for ASTA require additional improvements with regard to their loading capacity and stability. Methods: In this study, we developed lecithin nano-liposol (Lec NS) as a novel carrier of ASTA using a simple emulsion evaporation method. The physicochemical characteristics including hydrodynamic diameter, polydispersity index, surface charge and morphology were analyzed by DLS and TEM. The antioxidant activity of the ASTA-loaded Lec NS (ASTA@Lec NS) was evaluated using a DPPH radical scavenging assay and in vitro antioxidant assay. The study of in vitro wound healing efficacy was carried out to observe the beneficial effect of antioxidant activity of ASTA@Lec NS on cell migration. Results: ASTA@Lec NS showed improved stability and efficacy owing to improved aqueous solubility of ASTA inside Lec NS. Both in situ and in vitro antioxidant activities of ASTA@Lec NS were higher than that of bare ASTA and Lec NS. It also exhibited strong wound healing efficacy by regulation of ROS level in in vitro cell model. Conclusion: This study revealed that the encapsulation of ASTA into Lec NS using a wet phase transfer enhanced its physiological stability and bioavailability for effective scavenging of reactive oxygen species.
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