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Application of imine phenazine compound as rabies virus inhibitor

A rabies virus and compound technology, applied in the field of medicine, can solve problems such as disease-onset death, high price of immunoglobulin, and weak self-protection awareness

Active Publication Date: 2018-11-23
NAT INST FOR FOOD & DRUG CONTROL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to reports, about 2,000 people are infected with rabies every year. However, due to the lack of effective drugs and treatments, the fatality rate of rabies patients is almost 100%.
[0005] Biological products currently used to prevent and treat rabies mainly include vaccines and immunoglobulins, which are difficult to be widely used due to their high price and the need for low temperature storage
Especially in the rural areas of our country, many families have guard dogs, but few people immunize the dogs they raise, and their self-protection awareness is weak, and they are too close to the dogs. After being bitten by dogs and cats, some people are not vaccinated due to the high price of immunoglobulin and vaccines, which eventually lead to disease and death
However, chemical drugs can generally be placed at room temperature, are convenient to store, have low cost, and can be widely used nationwide. Moreover, the country has not included the prevention and control of rabies into the scope of major animal diseases. Therefore, it is imminent to find common clinical drugs against rabies virus.

Method used

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  • Application of imine phenazine compound as rabies virus inhibitor
  • Application of imine phenazine compound as rabies virus inhibitor
  • Application of imine phenazine compound as rabies virus inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Embodiment 1. Construction of pseudovirus

[0072] 1.1 Antiviral Drug Screening Principle Based on Pseudovirus

[0073] For an enveloped virus (eg, rabies virus), the process of cell entry is determined by its envelope protein, since the envelope is responsible for recognizing receptors on the surface of target cells and initiating the process of adsorption and penetration. Furthermore, the phenotypic mixing that occurs when two viruses co-infect a cell suggests that the envelope of one virus can be integrated on the particle surface of a different virus. Based on the above two points, a new technology—pseudovirus technology has been developed in the study of the process of virus invasion into cells and its tissue tropism and receptors.

[0074] The current pseudovirus refers to a retrovirus that can integrate the envelope glycoprotein of another different type of virus to form an envelope with an exogenous virus, and the genome maintains the genomic characteristics ...

Embodiment 2

[0092] Embodiment 2.RV-07 is to the evaluation of the inhibitory activity of rabies pseudovirus

[0093] In this embodiment, the rabies virus inhibitory activity of RV-07 (clofazimine national standard product, provided by the China National Institutes for Food and Drug Control Standard Material) was evaluated by using the rabies pseudovirus as described above.

[0094] Since the pseudovirus backbone plasmid pSG3Δenv.cmvFluc used in the present invention is derived from HIV, in order to exclude the possibility that the drug inhibits the pseudovirus by preventing the reverse transcription process of the backbone HIV, the present invention utilizes the rabies pseudovirus primary screening drug while utilizing A chimeric pseudovirus containing vesicular stomatitis virus (VSV) membrane protein was re-screened to exclude false positives. Calculate the ratio of the drug to the 50% inhibitory concentration (IC50) of the VSV membrane protein chimeric pseudovirus and the rabies virus m...

Embodiment 3

[0107] Cytotoxicity evaluation of embodiment 3.RV-07

[0108] In this embodiment, the influence of RV-07 (the national standard product of clofazimine, provided by the China Institute for Food and Drug Control Standard Materials) on cell viability was evaluated through the quantitative determination of ATP. The detection principle is as follows:

[0109] ATP is an indicator of metabolism in living cells, using CellTiter- Luminescence method cell viability detection kit, through the quantitative determination of ATP to detect the number of living cells in the culture after the action of drugs and cells, the cell lysis and the luminescent signal produced are proportional to the amount of ATP present, and the amount of ATP is directly related to the culture Proportional to the number of cells in . The 50% cytotoxic concentration (CC50) of the drug was calculated by the effect of the drug on the ATP luminescent signal in the cells. Calculate the ratio of the 50% cytotoxic conce...

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Abstract

The invention belongs to the technical field of medicines and particularly relates to application of an imine phenazine compound with a structure shown as a formula (I) and for preventing and / or treating rabies virus infection or diseases (for example, rabies) caused by the rabies virus infection. The application also relates to application of the imine phenazine compound for preparing a pharmaceutical composition for preventing and / or treating the rabies virus infection or the diseases (for example, the rabies) caused by the rabies virus infection. The formula (I) is shown in the description.

Description

technical field [0001] The invention belongs to the technical field of medicine. In particular, the present invention relates to the use of iminophenazine compounds having the structure of formula (I) for preventing and / or treating rabies virus infection or diseases caused by rabies virus infection (eg, rabies). The present application also relates to the use of iminophenazine compounds for preparing pharmaceutical compositions for preventing and / or treating rabies virus infection or diseases caused by rabies virus infection (eg, rabies). [0002] Background technique [0003] Rabies is a zoonotic infectious disease caused by rabies virus, almost all warm-blooded animals are susceptible, and dogs are the main host, playing an important role in the process of disease transmission. The main route of transmission is through animal bites, the virus in saliva enters the body through damaged skin, and other routes include the digestive tract and animal scratches. [0004] In ...

Claims

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Application Information

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IPC IPC(8): A61K31/498A61P31/14
CPCA61K31/498A61P31/14
Inventor 王佑春谢会刘强曹守春黄维金聂建辉赵晨燕
Owner NAT INST FOR FOOD & DRUG CONTROL
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