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The new application of compound arv-825 for the preparation of drugs for the prevention or treatment of African swine fever

A kind of ARV-825, African swine fever technology, applied in the field of compound ARV-825 for prevention or treatment of African swine fever, can solve problems such as economic loss, 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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  • The new application of compound arv-825 for the preparation of drugs for the prevention or treatment of African swine fever
  • The new application of compound arv-825 for the preparation of drugs for the prevention or treatment of African swine fever
  • The new application of compound arv-825 for the preparation of drugs for the prevention or treatment of African swine fever

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Effect of Compound ARV-825 on African Swine Fever Virus Infection Replication and Gene Transcription Expression

[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 ARV-825 (0.5 μM, 1 μM, 2 μM, 5 μM, 8 μM, 10 μM) for 16 h, and the infection control group treated the cells with DMSO (1%) for 16 h; Double-dilution ASFV CN / SC / 2019 strain (MOI=0.1), make 8 dilutions, each dilution repeats 8 wells, inoculate into 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 around monocytes and macrophages infected wi...

Embodiment 2

[0052] Example 2 Effect of compound ARV-825 on the expression levels of host inflammation-related factors

[0053] Porcine alveolar macrophages (PAM, 1 × 10 6 / well); the experimental group was treated with ARV-825 (0.5 μM) for 16 hours, and then infected with the ASFV CN / SC / 2019 strain (MOI=0.1); the blank control group was not treated; the compound ARV-825 alone was treated with ARV-825 (0.5μM) treated the cells for 16h; the virus alone infection group treated the cells with DMSO (1%) for 16h, and then directly infected the ASFV CN / SC / 2019 strain (MOI=0.1); the cells treated separately above After continuing to culture 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 expression difference of host inflammation-related factors was detected by Q-PCR method (same as in Example 1).

[0054] Wherein, the TNF-α primer sequence is: ...

Embodiment 3

[0059] Cytotoxicity of Example 3 Compound ARV-825

[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 / well), culture overnight, add different concentrations of ARV-825 (0.5μM, 1μM, 5μM, 10μM, 20μM, 40μM, 80μM, 160μM, 240μM) to the wells, and set blank wells (only containing medium), control Well (containing cells and medium), after the culture plate was incubated in the incubator for 16h, 10 μL of CCK-8 solution was added to each well of the plate, and the culture plate was incubated in the incubator for 1-4h, after reading Mix gently on a shaker before plating. 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 ARV-825 has little toxicity to cells, and even when the dose reaches 20 μM, the cell activity can still reac...

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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 ARV‑825 for preventing or treating African swine fever. The present invention unexpectedly finds that compound ARV-825 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 ARV-825 can significantly increase TNF after ASFV infection ‑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, the compound ARV‑825 can be used for the prevention or treatment of African swine fever.

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 ARV-825 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 A...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/551A61P31/20
CPCA61K31/551A61P31/20
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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