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Proteasom or ups inhibitor for treating infections with influenza viruses

A technology for viral infections, influenza viruses, applied in the field of proteasome inhibitors, global and topical proteasome inhibitors, medications in aerosol form, drugs for the prophylaxis and/or treatment of viral infections, able to resolve proteases not discussed The effect of proteasome inhibitors on influenza virus infection, the connection of influenza virus infection has not been reported, and the assembly and release of proteasome inhibitors on influenza virus have not been tested, so as to prevent further spread, reduce outbreaks, and prevent outbreaks

Inactive Publication Date: 2009-03-11
VIROLOGIK GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Likewise, the effectiveness of proteasome inhibitors in the treatment of influenza virus infection was not discussed
Also, it has not been tested whether proteasome inhibitors inhibit influenza virus assembly and release
Likewise, no link between influenza virus infection and UPS has been reported to date

Method used

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  • Proteasom or ups inhibitor for treating infections with influenza viruses
  • Proteasom or ups inhibitor for treating infections with influenza viruses
  • Proteasom or ups inhibitor for treating infections with influenza viruses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0111] Example 1: Proteasome inhibitors did not show any toxic side effects after treatment of mice with aerosol.

[0112] In order to investigate whether proteasome inhibitors have toxic side effects after administration in the form of aerosol, 6 mice were treated with 500 nM proteasome inhibitors, 3 times a day, for 5 days. Here, 2ml of proteasome inhibitors (500nM) were passed through a nebulizer (PARI ) to achieve the atomization effect. Each treatment lasts 10 minutes, and the treatment time is at 9:00, 12:00 and 15:00 respectively. In the experiment, 6 mice were selected, and the solvent (DMSO / H 2 O) Processing. To measure body temperature and physical activity in mice, a small sensor was implanted in the mice. And place the signal receiver board at the bottom of the squirrel cage, at this time the receiver will feed back the received signal to the computer, and analyze and process the data through specific data software.

[0113] After the sensor was implanted in ...

Embodiment 2

[0114] Example 2: During the observation period, proteasome inhibitors effectively prevented the replication of influenza virus in a concentration-dependent manner, and had no obvious toxic and side effects on host cells within the effective antiviral concentration range.

[0115] In order to investigate whether proteasome inhibitors inhibit the replication of influenza virus, human A549 lung epithelial cancer cells (Figure 2A, 2B) or Medinamy canine kidney (MDCKII) epithelial cancer cells (Figure 2C) were selected with given concentrations of protease They were pre-incubated for 1 hour with the body inhibitor, and then they were infected with an avian influenza virus strain (A / FPV / Bratislava / 79, H7N7) (multiple infection, (MOI)=0.01). A parallel experiment was carried out in which untreated cells were infected, specifically cells treated with dimethyl sulfoxide (DMSO) only. The substances used were: ps341 (10 nM and 100 nM), ps273 (10 nM and 100 nM), lactacystin (1 μM and 10 ...

Embodiment 3

[0119] Example 3: The antiviral effect of proteasome inhibitors on influenza virus does not depend on the mechanism of action of NF-κB.

[0120] In order to investigate whether the antiviral effect of proteasome inhibitors is rooted in the inhibition of NF-κB signaling pathway, the degradation of IκBα protein (inhibitor of κB) in the presence and absence of proteasome inhibitors was investigated. On the basis of , the TNFα-inducible activity of NF-κB was analyzed by Western blot. For this purpose, A549 cells (2×10 6 ) or HEK293 cells (4×10 6 ) were pre-incubated for 1 hour in different concentrations of proteasome inhibitors. Then, the above cells were treated with 20 ng / nl of TNFα for 15 minutes to induce the breakdown of IκBα. These cells were then incubated in 1xPBS and lysed. Wherein the protein concentration was determined by the Bradford protein assay (Biorad) and connected to each other as a line. Proteins were separated by SDS gel electrophoresis and transferred to ...

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PUM

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Abstract

The invention relates to compositions for the prophylaxis and / or treatment of viral infections, in particular of infections with influenza viruses which cause influenzal infections. The invention relates to compositions which comprise inhibitors of the ubiquitin-proteasome system, in particular proteasome inhibitors, as active ingredients. The present invention further relates to the systemic and topical, preferably the aerogenic administration of proteasome inhibitors. The active substance employed according to the invention as proteasome inhibitor can be employed with at least one further substance having antiviral activity for the prophylaxis and / or therapy of influenzavirus infections.

Description

technical field [0001] The present invention relates to medicaments for the prevention and / or treatment of viral infections, in particular to medicaments for infections caused by influenza viruses. The subject of the present invention is a medicament comprising as active ingredient an inhibitor of the ubiquitin-protease system, especially a proteasome inhibitor. The present invention also relates to overall and local administration of proteasome inhibitors, particularly preferably in the form of aerosols. The proteasome inhibitor active ingredient described in the present invention can be used together with at least one other substance with antiviral effect to prevent and / or treat influenza virus infection. Background technique [0002] 1. Influenza virus infection in animals and humans [0003] Infection by influenza viruses, that is, infections caused by influenza pathogens, poses a great threat to human and animal health. At the same time, not only is this infection ca...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P31/16A61K31/165A61K31/336A61P31/12A61K31/00A61K45/06A61K31/69
CPCA61K31/336A61K31/00A61K31/165A61K31/69A61K45/06A61P31/12A61P31/16A61P43/00A61K2300/00
Inventor 乌尔里希·舒伯特斯特凡·路德维希奥利弗·普兰茨
Owner VIROLOGIK GMBH
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