Application of 1,2,4triazolo4,3-bpyridazine derivatives in the preparation of anti-new coronavirus drugs

A pyridazine derivative and 3-B technology, applied in the field of medicine, can solve the problems of unbearable for patients, high cost, lack of curative effect in severe patients, etc., achieve wide application prospects, and suppress the effect of inflammatory factor storm

Active Publication Date: 2022-07-08
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Remdesivir is currently the most effective small-molecule drug for the treatment of new coronary pneumonia. However, although the compound has a significant antiviral effect in vitro experiments, it has not significantly inhibited the viral load in patients in clinical applications, and the drug can only Shorten the recovery time of mild patients, lack of curative effect on severe patients
At present, only adjuvant treatment methods such as respiratory therapy can be used for severe patients, supplemented by anti-inflammatory factor drugs and serum of recovered patients.
Except for Lianhua Qingwen Capsules, all currently used drugs for the treatment of new coronary pneumonia still face the disadvantages of high cost and unbearable for patients

Method used

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  • Application of 1,2,4triazolo4,3-bpyridazine derivatives in the preparation of anti-new coronavirus drugs
  • Application of 1,2,4triazolo4,3-bpyridazine derivatives in the preparation of anti-new coronavirus drugs
  • Application of 1,2,4triazolo4,3-bpyridazine derivatives in the preparation of anti-new coronavirus drugs

Examples

Experimental program
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Effect test

Embodiment 1

[0083] Example 1 Inhibitory effect of let-7 on SARS-CoV-2

[0084] The inventor's team predicted the potential miRNA action sites on SARS-CoV-2 through bioinformatics, screened out the target miRNA, and verified the effect of the target miRNA on SARS-CoV-2 by western blotting.

[0085] Bioinformatics prediction of miRNA and target gene interactions: Download the SARS-CoV-2 genome sequence from NCBI, and use RegRNA software to predict the potential miRNA action sites on SARS-CoV-2 online. The results indicated that let-7 has potential binding sites on the S and M genes of SARS-CoV-2 organisms.

[0086] To verify the interaction between miRNA and target genes: HEK293T cells were co-transfected with S or M protein expression plasmids and miRNA expression plasmids. 48h after transfection, cells were lysed for western blot analysis of protein expression levels.

[0087] Western blotting: After cells were lysed with lysis buffer containing SDS and mercaptoethanol, they were boiled ...

Embodiment 2

[0094] Example 2 Inhibitory effect of C1632 on SARS-CoV-2

[0095] C1632 is a let-7 agonist. In order to determine whether C1632 can inhibit the expression of S and M proteins of SARS-CoV-2 by regulating the level of let-7 expression in cells, the inventors treated cells with C1632 for 2 days and detected let-7 by QRT-PCR. -7 expression level.

[0096] The result is as image 3 shown. The results showed that C1632 treatment made let-7a-5p, let-7d-5p, let-7e-5p, let-7a-3p, let-7b-3p, let-7e-3p, let-7f-1 in HEK293T cells , let-7f-2, let-7g, let-7i and miR-98 were significantly upregulated ( image 3 middle A). Western blot showed that C1632 could significantly inhibit the exogenous S protein in HEK293T cells ( image 3 B) and M proteins ( image 3 expression in C).

[0097] In order to explore whether the let-7 agonist C1632 also has the function of regulating inflammatory factors, the effect of C1632 on the expression levels of let-7 and inflammatory factors in HEK293T, ...

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Abstract

The invention discloses the application of miRNA let-7 or its agonist in preparing a medicine for treating novel coronavirus SARS-CoV-2. The present invention also provides [1,2,4]triazolo[4,3-B]pyridazine derivatives represented by formula (I), pharmaceutically acceptable salts or polymorphs thereof in the preparation and treatment of novel coronavirus Virus SARS‑CoV‑2 drug use. The miRNA let-7 and its agonist provided by the present invention, the [1,2,4]triazolo[4,3-B]pyridazine derivatives represented by formula (I) can all be used as bifunctional targeted drugs to control viruses Proliferation while inhibiting the inflammatory factor storm to treat new coronary pneumonia has broad application prospects.

Description

technical field [0001] The technical field of medicine of the present invention, more particularly, relates to the application of 1,2,4-triazolo-4,3-B pyridazine derivatives in the preparation of anti-new coronavirus drugs. Background technique [0002] New coronary pneumonia has now entered the stage of a global pandemic. However, there is still no specific drug for new coronary pneumonia, especially the lack of effective treatment for severe patients, which is also the main reason for the high mortality rate of new coronary pneumonia. Inflammatory factor storm caused by viral infection is an important lethal factor for new coronary pneumonia. Blocking virus replication and controlling inflammatory factor storm are important directions for the development of specific drugs for new coronary pneumonia. [0003] Symptoms of COVID-19 are similar to the flu. Common symptoms include: fever (98.6%), fatigue (69.6%), dry cough (59.4%), myalgia and respiratory symptoms such as dyspn...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/5025A61K31/7088A61P31/14A61P11/00C07D487/04A61K48/00
CPCA61K31/5025A61K31/7088A61P31/14A61P11/00C07D487/04A61K2300/00Y02A50/30
Inventor 赵勇谢晨陈艳莲金和平
Owner SUN YAT SEN UNIV
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