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Application of tauroursodeoxycholic acid in drugs for resisting hand-foot-mouth virus and vesicular stomatitis virus

A technology of tauroursodeoxycholic acid and vesicular stomatitis virus, which is applied in the directions of antiviral agents, medical preparations containing active ingredients, pharmaceutical formulations, etc. and its mechanism

Active Publication Date: 2019-10-11
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Studies have found that TUDCA can inhibit the infection of influenza virus, Ebola virus and hepatitis B virus, but there is no report that TUDCA can inhibit the infection of hand, foot and mouth virus and vesicular stomatitis virus and its mechanism

Method used

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  • Application of tauroursodeoxycholic acid in drugs for resisting hand-foot-mouth virus and vesicular stomatitis virus
  • Application of tauroursodeoxycholic acid in drugs for resisting hand-foot-mouth virus and vesicular stomatitis virus
  • Application of tauroursodeoxycholic acid in drugs for resisting hand-foot-mouth virus and vesicular stomatitis virus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] [Example 1] TUDCA is to RD cell (human malignant embryonic rhabdomyosarcoma cell) toxicity test

[0080]MTT Cell Proliferation and Cytotoxicity Detection Kit is a classic cell proliferation and cytotoxicity detection kit, which is widely used in the detection of cell proliferation and cytotoxicity. MTT can be reduced by some dehydrogenases in the mitochondria to generate a crystalline deep purple product formazan (formazan), which can be completely dissolved in the presence of a specific solvent, and then the absorbance near the wavelength of 570nm can be measured by a microplate reader. The more and faster the cell proliferation, the higher the absorbance; the greater the cytotoxicity, the lower the absorbance.

[0081] The steps of TUDCA cytotoxicity test on RD are as follows:

[0082] 1) Preparation of MTT solution: Dissolve 25 mg of MTT in 5 ml of MTT solvent in the kit to prepare a 5 mg / ml MTT solution. It can be used immediately after preparation, or directly st...

Embodiment 2

[0090] [Example 2] TUDCA has a dose effect on the protective effect of EV71 infected cells

[0091] In the experimental group, TUDCA with a final concentration of 100 μM, 200 μM, 500 μM, 1000 μM and 3000 μM was added to the cell culture medium 2 hours before virus infection (-2hpi); DMSO control group (negative control group) was added 2 hours before virus infection ( -2 hpi) Add DMSO at final concentrations of 100 μM, 200 μM, 500 μM, 1000 μM and 3000 μM to the cell culture medium, respectively. Carry out virus infection afterwards, adopt EV71 (MOI=5) to infect RD cell 24 hours later, use MTT method to measure the protective effect of TUDCA to the RD cell infected by EV71, cell survival rate is the protection rate expressed by percentage. Three replicate holes were made for each concentration, and the average value was taken.

[0092] Table 2

[0093]

[0094]

[0095] The results showed that compared with the DMSO control group, the protective effect of TUDCA on RD ce...

Embodiment 3

[0096] [Example 3] The inhibitory effect of TUDCA on EV71 infection mainly occurs at the stage of EV71 invading cells

[0097] Virus infection is divided into the stage of extracellular adsorption and invasion into the cell, and the subsequent stage of replication, assembly and release in the cell.

[0098] 1. In order to determine the stage of TUDCA inhibition of EV71 infection, the experimental samples were treated with 1mM TUDCA in three time periods:

[0099] 1) -2~0hpi group: Add cell culture medium containing TUDCA 2 hours before virus infection to pretreat the cells, but remove the medium containing TUDCA during virus infection and replace with culture medium without TUDCA;

[0100] 2) 0-2hpi group: use the infection solution containing TUDCA only during the virus infection process (ie 0-2hpi), and then remove the infection solution, and the cell culture solution before or after this infection time does not contain TUDCA;

[0101] 3) 2-24hpi group: the virus infection ...

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Abstract

The invention discloses application of tauroursodeoxycholic acid in drugs for resisting a hand-foot-mouth virus and a vesicular stomatitis virus. The tauroursodeoxycholic acid inhibits the infection of host cells by the hand-foot-mouth virus and the vesicular stomatitis virus by altering the activity of the viruses themselves at the stage that the hand-foot-mouth virus and the vesicular stomatitisvirus adsorb and invade the host cells. The hand-foot-mouth virus is an EV71 virus and / or CA16 virus. The tauroursodeoxycholic acid can be used for preparing the drugs for resisting adsorption and invasion of the hand-foot-mouth virus and the vesicular stomatitis virus, especially drugs for a hand-foot-mouth disease caused by EV71 and CA16. The new phamaceutical value of TUDCA is found, and a newthought is found for virus resistance and prevention and / or treatment of virus adsorption and invasion.

Description

technical field [0001] The invention relates to the field of antiviral drugs, in particular to the application of tauroursodeoxycholic acid (TUDCA) in anti-hand-foot-mouth virus and vesicular stomatitis virus drugs. Background technique [0002] Hand, foot and mouth disease (HFMD) is a common infectious disease in children, which occurs in infants under 5 years old. Common symptoms of the disease are fever and rashes on the hands, feet, mouth and other parts. Some severe cases manifest as aseptic encephalitis, pulmonary edema, etc., and even lead to death. In May 2008, the Ministry of Health included HFMD in the statutory report of Class C infectious diseases. [0003] Enterovirus 71 (EV71) and Coxsackie A group 16 (CA16) are the most important pathogens causing HFMD. Among the HFMD cases diagnosed by laboratory etiology, the positive ratios of EV71, CA16 and other enteroviruses were 44%, 25% and 31%, respectively. Among them, EV71 positive accounted for 74% of severe cas...

Claims

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Application Information

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IPC IPC(8): A61K31/56A61P31/14
CPCA61K31/56A61P31/14
Inventor 吕颂雅刘勇陈倩
Owner WUHAN UNIV
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