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The new application of ml-60218 in the preparation of medicines for treating African swine fever

A ML-60218, 1. ML-60218 technology, applied in the field of African swine fever treatment, can solve the problem of not being able to inhibit the replication of HSV-1 virus, and achieve the effect of reducing virus titer and inhibiting replication

Active Publication Date: 2021-12-28
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

Wherein document (Melchjorsen J, et al.Early Innate Recognition of Herpes Simplex Virus in Human Primary Macrophages Is Mediated via the MDA5 / MAVS-Dependent and MDA5 / MAVS / RNA Polymerase III-Independent Pathways.) discloses RNA polymerase III inhibitor ML60218 There is no inhibition on the levels of interferon IFN-β and TNF-α after HSV-1 infection, that is, ML60218 cannot inhibit the replication of HSV-1 virus

Method used

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  • The new application of ml-60218 in the preparation of medicines for treating African swine fever
  • The new application of ml-60218 in the preparation of medicines for treating African swine fever
  • The new application of ml-60218 in the preparation of medicines for treating African swine fever

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1 Effect of ML-60218 on African swine fever virus infection replication and gene transcription expression

[0034] 1. Changes in African swine fever virus infection and replication

[0035] Porcine alveolar macrophages (PAM, 1 × 10 6 / well), the experimental group was treated with ML-60218 (50μM) for 2h, and then infected with ASFV CN / GS / 2018 strain (0.1MOI) for 6h, 12h, 24h; the control group was treated with DMSO (1%) for 2h, and then infected with ASFV CN / GS / 2018 strain (0.1MOI) 6h, 12h, 24h. Cells and supernatants from different treatments and different time points were collected, frozen and thawed three times at -80°C as samples, and serially diluted 10 times with serum-free RPMI 1640 to make 7 dilutions, each dilution repeated 8 wells , inoculated into PAM cells for culture, while adding porcine red blood cells; place the cell plate at 37°C, 5% CO 2 The conditions were cultured for 7 days, and the hematocyte adsorption reaction (HAD) in each cell cultur...

Embodiment 2

[0046] Example 2 Cytotoxicity of ML-60218

[0047] Using the established stable in vitro cell screening system, the cytotoxicity of the small molecule compound ML-60218 was detected by the CCK-8 method. Porcine alveolar macrophages (PAM, 2 × 10 5 / well), cultivated overnight, added different concentrations of ML-60218 (12.5μM 25μM 50μM 100μM 200μM) to the wells, and set blank wells (only containing medium), control wells (containing cells and medium), and the culture plate After incubating in the incubator for 2 hours, add 10 μL of CCK-8 solution to each well of the plate, incubate the plate in the incubator for 1-4 hours, and mix gently on a shaker before reading the plate. Then read the microplate reader to measure the absorbance at 450nm, and calculate the cell viability.

[0048] The result is as Figure 4 As shown, ML-60218 has less toxicity to cells and better safety.

[0049] In summary, the ML-60218 of the present invention can significantly inhibit the expression ...

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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 ML-60218 for preventing or treating African swine fever. The present invention unexpectedly found that ML-60218 can significantly inhibit the expression of African swine fever virus protein p30, prevent the virus from invading host cells, and can be used to inhibit the early infection of ASFV; and ML-60218 can significantly inhibit the replication of African swine fever virus, reduce the The virus titer after swine fever virus infection can be used as an inhibitor of African swine fever virus to prevent or treat 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 ML-60218 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 African s...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4155A61P31/20
CPCA61K31/4155A61P31/20
Inventor 郑海学李丹吴盼雪王延轶冉勇杨文萍张敬茹毅田宏杨帆张克山刘永杰
Owner LANZHOU INST OF VETERINARY SCI CHINESE ACAD OF AGRI SCI
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