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Application of ogdh inhibitors in the treatment of viral infectious diseases

An infectious disease, inhibitor technology, used in biotechnology and medicine

Active Publication Date: 2021-07-13
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] At present, there are no research reports on the role and regulation mechanism of the metabolic enzyme OGDH in the process of virus infection, and its therapeutic application in virus-related diseases at home and abroad.

Method used

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  • Application of ogdh inhibitors in the treatment of viral infectious diseases
  • Application of ogdh inhibitors in the treatment of viral infectious diseases
  • Application of ogdh inhibitors in the treatment of viral infectious diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0116] Example 1: Both RNA virus and DNA virus infection can inhibit the expression level of OGDH

[0117] The primary peritoneal macrophages of mice were isolated from C57BL / 6 small cells after intraperitoneal injection of 2ml of 3% thioglycolate (according to % is the ratio of m / v, dissolved in double distilled water, and then subjected to high-pressure sterilization). Rats (6-8 weeks old, male) were cultured in endotoxin-free high-glucose DMEM medium containing 10% fetal bovine serum (FBS).

[0118] RNA viruses used in this experiment: Vesicular Stomatitis Virus (VSV), Encephalomyocarditis virus (EMCV), Sendai virus (Sendai virus, SeV); and DNA viruses: Herpes simplex virus type 1, HSV-1) was purchased from ATCC, and its amplification method and infection cell conditions were in accordance with previous literature reports (Wang P et al., Science, 2017, 358(6366): 1051-1055; Liu S et al., Natureimmunology, 2018, 19(1 ):41-52).

[0119] The above-mentioned different RNA vir...

Embodiment 2

[0122] Example 2: OGDH can promote virus infection in murine and human cells

[0123] The primary peritoneal macrophages of mice were isolated from C57BL / 6 small cells after intraperitoneal injection of 2ml of 3% thioglycolate (according to % is the ratio of m / v, dissolved in double distilled water, and then subjected to high-pressure sterilization). Rats (6-8 weeks old, male) were cultured in endotoxin-free high-sugar DMEM medium containing 10% fetal bovine serum (FBS) (same as Example 1).

[0124] The siRNA used to interfere with the mouse OGDH gene was transfected with TransIT-siQUEST Transfection Reagent (purchased from Mirus Company) according to the operating instructions (transfection parameters for 12-well cell culture plate: 100 μl of serum-free medium, TransIT- siQUEST Transfection Reagent 3μl, 25nM final concentration of siRNA 2.8μl) into primary peritoneal macrophages. After 48 hours, Western blot was used to detect the OGDH protein expression level to verify the ...

Embodiment 3

[0131] Example 3: Small molecule inhibitors against OGDH can inhibit viral infection

[0132] The primary peritoneal macrophages of mice were isolated from C57BL / 6 small cells after intraperitoneal injection of 2ml of 3% thioglycolate (according to % is the ratio of m / v, dissolved in double distilled water, and then subjected to high-pressure sterilization). Rats (6-8 weeks old, male) were cultured in endotoxin-free high-sugar DMEM medium containing 10% fetal bovine serum (FBS) (same as Example 1).

[0133] By using two reported small-molecule inhibitors of OGDH to treat primary peritoneal macrophages of wild-type mice with different concentrations of pharmacological treatment, it was found that both of them could inhibit virus infection in a dose-dependent manner ( image 3 ). Two small molecule inhibitors (Succinyl phosphonate, SP) (product number: HY-12688) and CPI-613 (product number: HY-15453) were purchased from MedChemExpress Company, and the corresponding concentratio...

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Abstract

The present disclosure relates to the application of inhibitors of α-ketoglutarate dehydrogenase (OGDH) in the treatment of viral infectious diseases. Specifically, the present disclosure relates to the use of OGDH inhibitors in the preparation of products for the treatment of viral infectious diseases and / or diseases and / or symptoms associated with viral infections, and corresponding pharmaceutical compositions or kits thereof . The present disclosure can be used for suppressing and treating virus infection, especially for objects with abnormal natural immune function, and has broad application prospects.

Description

technical field [0001] This disclosure is in the fields of biotechnology and medicine. Specifically, the present disclosure relates to the application of inhibitors of α-ketoglutarate dehydrogenase (OGDH) in the treatment of viral infectious diseases. Background technique [0002] Viral infection can cause various diseases and threaten human health. Studying the mechanism of virus-host interaction will help to understand the process of viral infection and its regulatory molecular mechanism, and provide new drug targets for the prevention and treatment of viral infectious diseases. [0003] Innate immune receptors can activate the kinase TBK1 and transcription factor IRF3 in the downstream signaling pathway by recognizing the virus that infects the host cell, thereby inducing the body to produce interferon (Interferon, IFN) and activating the expression of antiviral effector genes to resist infection with the virus. Clear virus (Schneider WM et al., Annual review of immunol...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P31/12
CPCA61K45/00A61P31/12
Inventor 刘洋曹雪涛
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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