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Application of benidipine in the preparation of drugs for preventing and/or treating bunyavirus infectious diseases

A technology for bunya virus and infectious diseases, applied in the field of medicine, can solve the problems of large individual differences, difficult to popularize, limited curative effect, etc., and achieve the effect of strong antiviral activity, strong antiviral effect, and obvious technical effect.

Active Publication Date: 2021-09-21
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 the preparation of drugs for preventing and/or treating bunyavirus infectious diseases
  • Application of benidipine in the preparation of drugs for preventing and/or treating bunyavirus infectious diseases
  • Application of benidipine in the preparation of drugs for preventing and/or treating bunyavirus infectious diseases

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 12-16 hours, and treat with 10 μM, 20 μM, 30 μM, 40 μM, 50 μM, 60 μM, 70 μM, 80 μM, 90 and 100 μM Benidipine respectively, and each group has three duplicate 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 DMEM medium with 2% FBS. After 16 hours, the culture medium was 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 co...

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Abstract

The invention relates to the field of medicine, in particular, it provides an application of benidipine in the preparation of medicines for preventing and / or treating bunyavirus infectious diseases. The inventors have discovered for the first time that benidipine and its pharmaceutically acceptable derivatives can be used to prevent or treat infectious diseases caused by bunyavirus. The test results show that benidipine has strong antiviral activity against bunyavirus, can significantly reduce the death rate and body weight change of bunyavirus-infected mice, and shows strong antiviral activity at the cell and animal levels effect, with an obvious technical effect.

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 Patents(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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