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Medicinas Complementárias
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1.
Antiviral Res ; 99(3): 371-82, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23820269

RESUMEN

An influenza pandemic poses a serious threat to humans and animals. Conventional treatments against influenza include two classes of pathogen-targeting antivirals: M2 ion channel blockers (such as amantadine) and neuraminidase inhibitors (such as oseltamivir). Examination of the mechanism of influenza viral infection has shown that endosomal acidification plays a major role in facilitating the fusion between viral and endosomal membranes. This pathway has led to investigations on vacuolar ATPase (v-ATPase) activity, whose role as a regulating factor on influenza virus replication has been verified in extensive genome-wide screenings. Blocking v-ATPase activity thus presents the opportunity to interfere with influenza viral infection by preventing the pH-dependent membrane fusion between endosomes and virions. This study aims to apply diphyllin, a natural compound shown to be as a novel v-ATPase inhibitor, as a potential antiviral for various influenza virus strains using cell-based assays. The results show that diphyllin alters cellular susceptibility to influenza viruses through the inhibition of endosomal acidification, thus interfering with downstream virus replication, including that of known drug-resistant strains. In addition, combinatorial treatment of the host-targeting diphyllin with pathogen-targeting therapeutics (oseltamivir and amantadine) demonstrates enhanced antiviral effects and cell protection in vitro.


Asunto(s)
Antivirales/farmacología , Benzodioxoles/farmacología , Medicamentos Herbarios Chinos/farmacología , Inhibidores Enzimáticos/farmacología , Gripe Humana/enzimología , Lignanos/farmacología , Orthomyxoviridae/efectos de los fármacos , ATPasas de Translocación de Protón Vacuolares/antagonistas & inhibidores , Amantadina/farmacología , Animales , Quimioterapia Combinada , Endosomas/virología , Humanos , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Magnoliopsida/química , Fusión de Membrana/efectos de los fármacos , Orthomyxoviridae/fisiología , Oseltamivir/farmacología , ATPasas de Translocación de Protón Vacuolares/metabolismo , Replicación Viral/efectos de los fármacos
2.
Antiviral Res ; 88(1): 25-30, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20603153

RESUMEN

Feline infectious peritonitis (FIP) is a fatal disease in domestic and nondomestic felids caused by feline coronavirus (FCoV). Currently, no effective vaccine is available for the prevention of this disease. In searching for agents that may prove clinically effective against FCoV infection, 16 compounds were screened for their antiviral activity against a local FCoV strain in Felis catus whole fetus-4 cells. The results showed that Galanthus nivalis agglutinin (GNA) and nelfinavir effectively inhibited FCoV replication. When the amount of virus preinoculated into the test cells was increased to mimic the high viral load present in the target cells of FIP cats, GNA and nelfinavir by themselves lost their inhibitory effect. However, when the two agents were added together to FCoV-infected cells, a synergistic antiviral effect defined by complete blockage of viral replication was observed. These results suggest that the combined use of GNA and nelfinavir has therapeutic potential in the prophylaxis and treatment of cats with early-diagnosed FIP.


Asunto(s)
Antivirales/farmacología , Coronavirus Felino/efectos de los fármacos , Galanthus , Lectinas de Unión a Manosa/farmacología , Nelfinavir/farmacología , Lectinas de Plantas/farmacología , Animales , Antivirales/uso terapéutico , Gatos , Células Cultivadas , Coronavirus Felino/fisiología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Peritonitis Infecciosa Felina/tratamiento farmacológico , Peritonitis Infecciosa Felina/virología , Feto , Lectinas de Unión a Manosa/uso terapéutico , Pruebas de Sensibilidad Microbiana , Nelfinavir/uso terapéutico , Lectinas de Plantas/uso terapéutico , Replicación Viral/efectos de los fármacos
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