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Small molecule inhibitor of Ebola pseudovirus

A technology of Ebola virus and inhibitors, applied in the field of small molecule inhibitors of Ebola pseudoviruses, which can solve the problems of unapproved vaccines and drugs on the market

Inactive Publication Date: 2018-05-11
INST PASTEUR OF SHANGHAI CHINESE ACADEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Ebola virus disease is still a very serious global public health problem, but so far there are no vaccines and drugs approved for marketing, and the development of antiviral drugs is imminent

Method used

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  • Small molecule inhibitor of Ebola pseudovirus
  • Small molecule inhibitor of Ebola pseudovirus
  • Small molecule inhibitor of Ebola pseudovirus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] The inhibitory effect of embodiment 1dPPA to Zaire type Ebola pseudovirus

[0071] dPPA can inhibit Zaire-type Ebola pseudovirus, and its EC 50 is 0.13 μM. And it does not show cytotoxicity at the highest tested concentration (25 μM). dPPA was unable to inhibit the infection of cells by vesicular stomatitis pseudovirus, and only showed a slight inhibitory effect at the highest tested concentration.

[0072] figure 1 .dPPA inhibits Zaire-type Ebola pseudovirus. A. Add 2-fold diluted dPPA to Vero cells, add Zaire-type Ebola pseudovirus and culture for 72 hours, then use the Bright-Glo kit to detect fluorescence (luciferase), and test the effect of dPPA on Zaire-type Ebola Inhibitory effect of pseudoviruses. B. Add 2-fold diluted dPPA to Vero cells, add the culture medium for 72 hours, and then use the CellTiter-Glo kit to detect the cell viability and test the toxicity of dPPA to the cells. Add 2-fold diluted dPPA to C.Vero cells, add vesicular stomatitis pseudoviru...

Embodiment 2

[0075] The inhibitory effect of embodiment 2 Kamara element (Rottlerin) to Zaire type Ebola pseudovirus

[0076] Rottlerin inhibits Zaire-type Ebola pseudovirus entry into cells, EC 50 is 0.96μM, and can also inhibit the infection of cells with vesicular stomatitis pseudovirus, and its EC 50 is 1.62 μM. It does not exhibit cytotoxicity at concentrations below 1.85 μM.

[0077] image 3 Inhibition of Zaire-type Ebola pseudoviruses by kamalatin. A. Add 2-fold diluted camarasin to Vero cells, add Zaire type Ebola pseudovirus and cultivate for 72 hours, then use Bright-Glo kit to detect fluorescence (luciferase), and test the effect of camarasin on Zaire Inhibitory effect of Il-type Ebola pseudovirus. B. Add 2-fold diluted Kamara to the Vero cells, add the culture medium for 72 hours, and use the CellTiter-Glo kit to detect the cell viability and test the toxicity of Kamara to the cells. C. Add 2-fold diluted camarasin to Vero cells, add vesicular stomatitis pseudovirus and ...

Embodiment 3

[0078] Embodiment 3 Galangin (Galangin) inhibits Zaire type Ebola pseudovirus

[0079] Galangin (Galangin) inhibits Zaire-type Ebola pseudovirus entry into cells, EC 50 It is 10.05μM, and it can also inhibit the infection of cells with vesicular stomatitis pseudovirus, and its EC 50 is 10.07 μM. No cytotoxicity was exhibited at the highest concentration tested (25 μM).

[0080] Figure 4 Inhibition of Zaire-type Ebola pseudovirus by galangin. A. Add 2-fold diluted galangin to Vero cells, add Zaire type Ebola pseudovirus and culture for 72 hours, then use Bright-Glo kit to detect fluorescence (luciferase), test the effect of galangin on Zaire Inhibitory effect of type Ebola pseudovirus. B. Add 2-fold diluted galangin to Vero cells, add to the medium and culture for 72 hours, then use the CellTiter-Glo kit to detect the cell survival rate, and test the toxicity of galangin to the cells. Add 2-fold diluted galangin to C.Vero cells, add vesicular stomatitis pseudovirus and c...

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Abstract

The invention provides a small molecule inhibitor of Ebola pseudovirus, particularly small molecule inhibitor of Ebola pseudovirus, wherein the small molecule inhibitor is selected from dPPA, mallotoxin, galangin, epigallocatechin, piceatannol and chrysin. According to the present invention, the experimental results show that the inhibitor can effectively inhibit the entry of Ebola virus into cells.

Description

technical field [0001] The invention belongs to the field of biotechnology, in particular, the invention relates to a small molecule inhibitor of Ebola pseudovirus. Background technique [0002] Ebola virus disease is a severe infectious disease caused by Ebola virus, which first broke out in Zaire and Sudan in central Africa in 1976. Ebola virus belongs to Filoviridae family (Filoviridae), its shape includes rod shape, filament shape, and "L" shape, the average length of virion particles is 1000nm, and the diameter is 70-90nm. It has been identified Ebola virus includes 5 species, Zaire ebolavirus, Sudan ebolavirus, Reston ebolavirus, Tai Forest ebolavirus and Bundibugyo type (Bundibugyo ebolavirus), of which the Zaire ebolavirus causes the most severe disease. Except for the Reston subtype virus, which is not pathogenic to humans, the other 4 subtypes are fatal to humans. Ebola virus disease can cause a fatality rate of up to 90%. Since the outbreak of Ebola virus diseas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/216A61K31/352A61K31/353A61K31/05A61P31/14
CPCA61K31/05A61K31/216A61K31/352A61K31/353
Inventor 邹罡蓝柯王一卓
Owner INST PASTEUR OF SHANGHAI CHINESE ACADEMY OF SCI
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