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Application of Triapine in treating African swine fever virus infection

A technology of African swine fever virus and its use, which is applied in the field of medicine, can solve the problems of research and disclosure of the therapeutic effect of Triapine on African swine fever virus, and achieve strong anti-African swine fever virus activity, high selectivity coefficient, and enhanced The effect of the treatment effect

Pending Publication Date: 2022-05-27
HARBIN VETERINARY RES INST CHINESE ACADEMY OF AGRI SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In the prior art, there is no research and disclosure on the therapeutic effect of Triapine on African swine fever virus

Method used

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  • Application of Triapine in treating African swine fever virus infection
  • Application of Triapine in treating African swine fever virus infection
  • Application of Triapine in treating African swine fever virus infection

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0051] The preparation template described in step S101 is: the ASFV ribose nucleotide reductase small subunit full-length protein sequence template is the mouse R2 ribose nucleotide reductase with the highest matching degree with F334L retrieved in PDB bank, according to the matching length, Coincidence rate and positive rate sorting; download its PDB format and import to MOE, retain A chain and Co 2+ ;

[0052] The sequence alignment described in step S101 is: the ASFV ribonucleotide reductase small subunit gene UniProt ID:P42492 is imported into the MOE, and the structural template is used for alignment, and the sequence overlap and similarity are calculated;

[0053] The homology modeling described in step S101 is: according to the standard homology modeling program, Co. 2+ As the construction environment, block the C-terminal and N-terminal modeling, and generate the intermediate model by sampling the main chain and side chain; fine-tune it through the force field Amber12...

Embodiment 1

[0059] Drug screening method for African swine fever virus ribonucleotide reductase inhibitors

[0060] Step 1: Construction of ASFV ribonucleotide reductase small subunit model: sequence identification, template preparation, sequence alignment and homology model modeling, homology model quality evaluation.

[0061] The encoding gene of the ASFV ribonucleotide reductase small subunit is F334L (UniProt ID: P42492), which is downloaded from UniProt (http: / / www.uniprot.org) and saved in FASTA format.

[0062] The described ASFV ribose nucleotide reductase small subunit full-length protein sequence template is to retrieve the mouse R2 ribose nucleotide reductase (PDB ID: 1H0N) with the highest matching degree with F334L in PDB bank, according to the matching length ( 307 bases), coincidence rate (132 out of 307), and positive rate (184 out of 307). Download its PDB format and import it into the Molecular Operating Environment (MOE, version 2019), retaining the A-chain (R2 ribonuc...

Embodiment 2

[0070] Screening of Triapine for Inhibiting therapeutic Drugs of African Swine Fever Virus Infection

[0071] By measuring CC 50 To evaluate the toxicity of Triapine to cells: 4 x 10 5 Pig alveolar macrophages (porcine alveolar macrophages, PAM) were seeded in a 96-well plate at a density of 1 / well and incubated for 24h.

[0072] Triapine was dissolved in DMSO to form a 1 mM solution, then diluted to 0.2 mM in 1640 medium containing 10% FBS and 2% dual-antibody SP (penicillin and streptomycin) as the initial concentration, and then diluted 2-fold in sequence to 8 gradients with 3 replicate wells for each gradient.

[0073] After culturing the cells for 24 hours, discard the cell culture supernatant, add 100 μL / well of the diluted drug, put it in a cell incubator for 72 hours, and use the WST-1 cytotoxicity detection reagent (Biyuntian, product number: C0036L) to determine its cell activity. Calculate the half cytotoxic concentration CC of Triapine 50 . The results are sho...

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Abstract

The invention relates to the technical field of medicines, in particular to application of Triapine to treatment of African swine fever virus infection. The invention discloses application of Triapine and salt forms, hydrates, solvates and isotope substitutes thereof in preparation of drugs for treating African swine fever viruses. The invention has the following advantages: (1) Triapine has low toxicity to cells and is safe; and (2) Triapine has a good antiviral effect and can effectively treat African swine fever virus infection. (3) the selectivity coefficient is high, and safety is realized. And (4) the composition can be combined for use to enhance the treatment effect of African swine fever virus infection.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of Triapine for treating African swine fever virus infection. Background technique [0002] African swine fever is a highly contagious disease caused by a large double-stranded DNA virus (African swine fever virus), and the mortality rate of domestic pigs after infection is close to 100%. African swine fever virus replicates mainly in the cytoplasm of macrophages and is the only member of the Asfivirus genus of the Asfarviridae family. The natural hosts of the virus include wild warthogs, ticks and bird arthropods, and not only can survive in frozen meat for a long time , even in the in vitro environment can survive for a long time, therefore, the virus is difficult to completely eradicate under natural conditions. The African swine fever virus epidemic has been circulating in pig herds on the African continent for decades, it has also affected Spain, Portugal, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/44A61P31/20G16B30/10
CPCA61K31/44A61P31/20G16B30/10Y02A50/30
Inventor 翁长江步志高郑君李婷婷魏文娟黄韬李江南黄丽张朝霞
Owner HARBIN VETERINARY RES INST CHINESE ACADEMY OF AGRI SCI
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