A small molecule inhibitor of Ebola pseudovirus

An Ebola virus and inhibitor technology, applied in the field of small molecule inhibitors of Ebola pseudovirus, can solve problems such as unapproved vaccines and drugs

Active Publication Date: 2019-07-19
中国科学院上海免疫与感染研究所
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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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  • A small molecule inhibitor of Ebola pseudovirus
  • A small molecule inhibitor of Ebola pseudovirus
  • A small molecule inhibitor of Ebola pseudovirus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Peptokomycin can inhibit the infection of cells by Zaire Ebola pseudovirus, and its EC 50 was 2.38 μM. And it does not show cytotoxicity at the highest tested concentration (125 μM). Peptokomycin was not able to inhibit the infection of cells by vesicular stomatitis pseudovirus.

[0093] Figure 1. Peptokomycin inhibits the infection of cells by Zaire-type Ebola pseudovirus. Figure 1A Add 3-fold diluted peptokomycin to Vero cells, add Zaire-type Ebola pseudovirus and culture for 72 hours, then use the Bright-Glo kit to detect luciferase, and test the effect of peptokomycin on Zaire Inhibitory effect of Ebola pseudovirus infection. Figure 1B Add 3-fold diluted peptokomycin to the 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 peptokomycin to the cells. Figure 1C Add 3-fold diluted pepticomycin to Vero cells, add vesicular stomatitis pseudovirus and culture for 72 hours, then...

Embodiment 2

[0098] Peptokomycin had no inhibitory effect on enterovirus 71 and was not cytotoxic to RD cells at a concentration of 125 μM.

[0099] Figure 3 Pepticocomycin does not inhibit enterovirus type 71. Figure 3A Vero cells were infected with EV71 with a multiple of infection (MOI) of 0.1, and pepticomycin at concentrations of 10 μM, 30 μM, and 100 μM were added, and the supernatant was collected after 42 hours of incubation, and the virus titers were determined by plaque formation assay. Spend. The data in the figure are from two independent parallel experiments, and the error bars represent the standard deviation of two parallel experiments. Figure 3B RD cells were added 3-fold diluted peptokomycin, added to the culture medium and cultured for 96 h, and the cell viability was detected by the CellTiter-Glo kit to detect the effect of peptokomycin on the cells. The data in the figure are from two independent parallel experiments, and the error bars represent the standard devia...

Embodiment 3

[0101] Peptokomycin prevents adsorption of Zaire-type Ebola pseudoviruses to cells.

[0102] Figure 4 Peptokomycin prevents adsorption of Zaire-type Ebola pseudoviruses to cells. Add pepticomycin with a concentration of 10 μM, 100 μM, and DMEM containing 2% FBS and 1% P / S to the pseudovirus and cells according to three different treatments before adsorption, during infection and after adsorption, and culture for 72 hours Afterwards, the Bright-Glo kit was used to detect the luciferase, and the effect of peptokomycin on different stages of virus entry into cells was evaluated. The data in the figure are from two independent parallel experiments, and the error bars represent the standard deviation of two parallel experiments. Results were processed using Graphpad Prism5. Experimental results showed that pepticomycin could prevent Zaire-type Ebola pseudovirus from adsorbing to cells, but it could not work after pseudovirus was adsorbed to cells.

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Abstract

The present invention provides an Ebola pseudovirus small molecule inhibitor, specifically oxeladin, teicoplanin, and other small molecule compounds capable of inhibiting Ebola pseudovirus. According to the present invention, the cell survival experiment results show that the compounds does not have cytotoxicity.

Description

technical field [0001] The invention belongs to the field of biomedicine, 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 disease ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/135A61K38/14A61P31/14C12N5/00
Inventor 邹罡艾德铭王一卓
Owner 中国科学院上海免疫与感染研究所
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