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Novel application of compound zl0580 for preparing drugs for preventing or treating African swine fever

An African swine fever and African swine fever virus technology, applied in the field of African swine fever treatment, can solve problems such as economic losses, inability to meet large-scale pig breeding, and achieve the effect of enhancing immune response

Active Publication Date: 2021-06-08
LANZHOU INST OF VETERINARY SCI CHINESE ACAD OF AGRI SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since there are still no effective vaccines and specific therapeutic drugs, once the African swine fever epidemic occurs, it can only be controlled by means of culling, but this method not only leads to economic losses, but also cannot meet the needs of large-scale pig raising in my country

Method used

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  • Novel application of compound zl0580 for preparing drugs for preventing or treating African swine fever
  • Novel application of compound zl0580 for preparing drugs for preventing or treating African swine fever
  • Novel application of compound zl0580 for preparing drugs for preventing or treating African swine fever

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 The effect of compound ZL0580 on the replication of African swine fever virus infection and the transcription and expression of genes

[0039] 1. Changes in African swine fever virus infection and replication

[0040] Porcine alveolar macrophages (PAM, 2 × 10 5 / well), the experimental group treated the cells with different concentrations of ZL0580 (0.5 μM, 1 μM, 2 μM, 5 μM, 8 μM, 10 μM) for 16 hours, and the infection control group treated the cells with DMSO (1%) for 16 hours; serially diluted 10 times with PBS ASFV CN / SC / 2019 strain (MOI=0.1), make 8 dilutions, repeat 8 wells for each dilution, inoculate PAM cells for culture, and add porcine red cells at the same time; place the cell plate at 37°C, 5%CO 2 The conditions were cultured for 3-6 days, and the hematocyte adsorption reaction (HAD) in each cell culture well was observed every day.

[0041] The hematocyte adsorption reaction (HAD) is based on the phenomenon that porcine erythrocytes will adsorb ...

Embodiment 2

[0052] Example 2 Effect of Compound ZL0580 on Expression Levels of Host Inflammation-Related Factors

[0053] Porcine alveolar macrophages (PAM, 1 × 10 6 / well); the experimental group was treated with ZL0580 (10 μM) for 16 hours, and then infected with ASFV CN / SC / 2019 strain (MOI=0.1); the blank control group was not treated; the compound ZL0580 treatment group was treated with ZL0580 (10 μM) The cells were treated with DMSO (1%) for 16 hours in the virus alone infection group, and then directly infected with the ASFV CN / SC / 2019 strain (MOI=0.1); the uninfected control group was treated with DMSO (1%) for 16 hours; After the above separately treated cells were cultured for 48 hours, the cell culture was collected, the cells were washed once with PBS, centrifuged, and the supernatant was discarded. Total RNA was extracted, and after cDNA was reverse transcribed, the difference in expression of host inflammation-related factors was detected by Q-PCR method (same as above).

...

Embodiment 3

[0059] The cytotoxicity of embodiment 3 compound ZL0580

[0060] By constructing a stable in vitro cell screening system, the cytotoxicity of the small molecule compound ARV-825 was detected by the CCK-8 method. Porcine alveolar macrophages (PAM, 2 × 10 5 Cultivate overnight, add different concentrations of ZL0580 (0.5 μM, 1 μM, 5 μM, 10 μM, 20 μM, 40 μM, 80 μM, 160 μM, 240 μM) to the wells, set blank wells (only containing medium), and control wells ( containing cells and medium), incubate the culture plate in the incubator for 16 hours, add 10 μL of CCK-8 solution to each well of the plate, incubate the culture plate in the incubator for 1-4 hours, read the plate Beforehand, mix gently on a shaker. Then read the microplate reader to measure the absorbance at 450nm, and calculate the cell viability.

[0061] The result is as Figure 5 As shown, the compound ZL0580 has little toxicity to cells, and even when the dose reaches 20 μM, the cell activity can still reach more th...

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Abstract

The invention belongs to the technical field of treating African swine fever, and in particular relates to a new application of compound ZL0580 for preventing or treating African swine fever. The present invention unexpectedly finds that compound ZL0580 can significantly inhibit the RNA and protein expression levels of p30 and p72 in ASFV, prevent the virus from invading host cells, and can be used to inhibit the early infection of ASFV; and compound ZL0580 can significantly increase TNF-α, NF ‑κB, IL‑1β, IL‑8 and other gene expression levels, up-regulate the transcription levels of TNF‑α, NF‑κB, IL‑1β, IL‑8, and enhance the immune response; therefore, compound ZL0580 can be used to prevent or treat African pigs plague.

Description

technical field [0001] The invention belongs to the technical field of treating African swine fever, and in particular relates to a new application of compound ZL0580 for preventing or treating African swine fever. Background technique [0002] African swine fever (African swine fever, ASF) is caused by the infection of African swine fever virus (ASFV), and is characterized by fever and hemorrhage in pigs. The fatality rate for domestic pigs is as high as 100%. . The disease first broke out in Kenya in 1921 and subsequently became widespread among domestic and wild pigs throughout Africa. It was introduced into Europe in the 1950s, and it took 40 years to eliminate the disease throughout Europe. However, the disease was introduced to Georgia from East Africa again in 2007, and then spread widely in Eastern Europe, and in 2017, it was introduced to Irkutsk in the Russian Far East. In early August 2019, researcher Hu Rongliang took the lead in reporting the first case of Af...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/401A61P31/20
CPCA61K31/401A61P31/20
Inventor 牛庆丽杨吉飞赵亚茹刘志杰关贵全罗建勋殷宏
Owner LANZHOU INST OF VETERINARY SCI CHINESE ACAD OF AGRI SCI
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