Application of benidipine in preparing drug for preventing and/or treating infectious diseases caused by Bunya viruses

A bunya virus, infectious disease technology, applied in the field of medicine, can solve the problems of large individual differences, limited curative effect, difficult to promote, etc., achieve strong antiviral activity, strong antiviral effect, reduce mortality and weight changes. Effect

Active Publication Date: 2019-09-17
WUHAN INST OF VIROLOGY CHINESE ACADEMY OF SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the treatment methods for bunyavirus infection are also quite limited. The main treatment methods are symptomatic supportive treatment and broad-spectrum antiviral therapy. The curative effect is limited, individual differences are large, and it is difficult to promote

Method used

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  • Application of benidipine in preparing drug for preventing and/or treating infectious diseases caused by Bunya viruses
  • Application of benidipine in preparing drug for preventing and/or treating infectious diseases caused by Bunya viruses
  • Application of benidipine in preparing drug for preventing and/or treating infectious diseases caused by Bunya viruses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Cytotoxicity detection of the target compound Benidipine

[0052] The cytotoxicity of Benidipine was tested in Vero cells. Vero cells by 1 x 10 4 Cells / well were seeded in 96-well cell culture plates at 37°C, 5% CO 2 Cultivate in the incubator for 12-16h, and treat with 10μM, 20μM, 30μM, 40μM, 50μM, 60μM, 70μM, 80μM, 90 and 100μM Benidipine respectively, and each group has three replicate wells, and the control group is added with the same amount of dimethyl Sulfoxide (DMSO). After 24 hours of drug action, use MTT staining to detect OD 492nm , to analyze cell viability, tested as figure 1 Shown, CC of Benidipine 50 is 96.92 μM. In the following examples, the concentration of Benidipine used is 10 μM, which is within the safe and non-toxic range.

Embodiment 2

[0054] Detection of antiviral activity of target compound Benidipine against SFTSV

[0055] Vero cells by 2 x 10 5 Cells / well were seeded in 24-well cell culture plates at 37°C, 5% CO 2 Cultivate in an incubator for 12-16 hours, and treat with Benidipine at a concentration of 1 μM, 5 μM, 10 μM, 20 μM and 40 μM, and add the same volume of DMSO to the negative control. After incubation for 1 hour, they were infected with SFTSV. After incubation at 37°C for 1 hour, the medium was replaced with 2% FBS DMEM medium. After 16 hours, the effect of Benidipine on inhibiting virus replication was detected by titer, and the results were as follows: figure 2 As shown, under different concentration conditions, the compound Benidipine has a significant inhibitory effect on the replication of SFTSV. Further inhibition of SFTSV IC by Benidipine 50 testing, the result is image 3 As shown in the inhibition curve of SFTSV, Benidipine significantly inhibited the activity of SFTSV, and its IC...

Embodiment 3

[0057] The effect of the target compound Benidipine on the replication of other bunyaviruses

[0058] Vero cells by 2 x 10 5 Cells / well were seeded in 24-well cell culture plates at 37°C, 5% CO 2 Cultivate in an incubator for 12-16 hours, and treat with Benidipine at a concentration of 1 μM, 5 μM, 10 μM, 20 μM and 40 μM, and add the same volume of DMSO to the negative control. After incubation for 1 hour, they were infected with Gourtu virus (GTV) and Heartland virus (HRTV), which belong to the genus Phlebovirus, respectively. After incubation at 37°C for 1 hour, the medium was replaced with 2% FBS DMEM medium. After 16 hours, passed Real-time fluorescent quantitative PCR (qPCR) method detects the effect of Benidipine inhibiting virus replication, such as Figure 4 As shown (wherein, Figure A is the effect of Benidipine on the replication of GTV, and Figure B is the effect of Benidipine on the replication of HRTV), under different concentration conditions, the compound Benid...

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Abstract

The invention relates to the field of medicine, and particularly provides application of benidipine in preparing a drug for preventing and / or treating infectious diseases caused by Bunya viruses. It is discovered for the first time that the benidipine and pharmaceutically acceptable derivatives thereof can be used for preventing or treating the infectious diseases caused by the Bunya viruses. Experimental results show that the benidipine has strong antiviral activity against the Bunya viruses, can significantly reduce the mortality and body weight change of mice infected by the Bunya viruses, shows a strong antiviral effect at the cell and animal levels, and has obvious technical advantages.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of benidipine in the preparation of drugs for preventing and / or treating bunyavirus infectious diseases. Background technique [0002] Benidipine is (±)-2,6,-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylic acid, 3-(1 -Benzyl-3-piperidinyl) ester-5-methyl ester, which was successfully developed by Kyowa Hakko in 1981, and was approved by the U.S. Food and Drug Administration (Food and Drug Administration) in 1991. DrugAdministration, FDA) approved formal clinical use. For decades, benidipine has a good effect in the treatment of essential hypertension and other aspects. The structural formula of benidipine is as follows: [0003] [0004] Bunya virus (Bunya virus) is a spherical, enveloped and segmented negative-sense RNA virus of the order 1. Natural infection is found in many vertebrates and arthropods (mosquitoes, ticks, sandflies, etc.), and it can...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4545A61P31/14
CPCA61K31/4545A61P31/14
Inventor 彭珂李淑芬肖庚富刘玮陈远侨张磊砢黎浩张玉兰万伟玮
Owner WUHAN INST OF VIROLOGY CHINESE ACADEMY OF SCI
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