Application of adenosine kinase inhibitor in preparation of anti-coronavirus preparation

A technology of coronavirus and adenosine kinase, which is applied in the field of biomedicine, can solve the problems of reducing the ratio and different biological activities, and achieve the effect of inhibiting replication

Active Publication Date: 2021-12-31
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, Meng Xiangzhi (Meng Xiangzhi. Research on the effect of Iodotubercidin loaded with CD44-targeted nanoliposomes on breast cancer tumor stem cells [D]. Nankai University) found that 5-iodotubercidin can reduce the MDA- The proportion of side p...

Method used

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  • Application of adenosine kinase inhibitor in preparation of anti-coronavirus preparation
  • Application of adenosine kinase inhibitor in preparation of anti-coronavirus preparation
  • Application of adenosine kinase inhibitor in preparation of anti-coronavirus preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The establishment of embodiment 1 cell level CoV-RdRp-Gluc reporter system

[0035]In this example, a luciferase reporter system specifically activated by the new coronavirus SARS-CoV-2RdRp, referred to as CoV-RdRp-Gluc, was established. Insert the Gaussia luciferase (Gluc) coding sequence (as shown in SEQ ID NO: 1) between the 5'UTR and 3'UTR of the new coronavirus, and then insert it into the pRetroX-Tight-Pur (Clontech) vector BamHI-HF (#R3136L , NEB) and Notl (NotI-HF, NEB) sites, using forward primer (5′-GGCGGATCCATTAAAGGTTTATAC-3′) and reverse primer (5′-TTAGCGGCCGCGTCATTCTCCCTAAGAA-3′), the pCoV-Gluc plasmid was constructed . Under the action of CMV promoter, the positive chain Gluc (mRNA) is transcribed and translated to produce Gluc protein. When the new coronavirus RNA-dependent RNA polymerase (nsp12) is expressed in the system at the same time, RdRp first uses the positive-strand Gluc as a template to synthesize the negative-strand vRNA, and then the vRNA i...

Embodiment 2

[0046] Example 2 Using the CoV-RdRp-Gluc reporter system to test the adenosine kinase inhibitor (5-iodotuberculin)

[0047] Will 2.5×10 5 Each / mL HEK 293T cell suspension was inoculated in a 6-well plate at 2 ml per well. When the cells grow to 80%, the HEK 293T cell group is co-transfected with 10ng of the pCoV-Gluc constructed in Example 1, 200ng of the eukaryotic codon-optimized plasmid pCOVID19-nsp12, and 600ng of the eukaryotic codon-optimized plasmid pCOVID19-nsp7 per well. and 600ng of eukaryotic codon-optimized plasmid pCOVID19-nsp8 plasmid. Four hours after transfection, the medium was replaced with DMEM medium containing 10% fetal bovine serum (FBS), and the culture was continued for 12 hours. Digest the cells in the six-well plate to make a cell suspension, press 1.0×10 4 HEK293T cells / ml were seeded in a 96-well plate, 100 μL per well. 1 μL of the compound 5-iodotubercidin (compound of formula I) and remdesivir at a concentration of 10 μM were added to each wel...

Embodiment 3

[0049] Example 3 5-iodotuberculin inhibits the transcriptional activity of SARS-CoV-2RdRp at the mRNA level

[0050] Detecting the effect of 5-iodotubercidin on SARS-CoV-Gluc at the mRNA level can further confirm the effect of 5-iodotubercidin on the transcriptional activity of SARS-CoV-2 RdRp. The present invention adopts qRT-PCR method to detect the inhibitory situation of 5-iodo-tubercidin on SARS-CoV-2RdRp at the mRNA level.

[0051] will be 2.5×10 5Each / mL HEK 293T cell suspension was inoculated in a 6-well plate at 2 ml per well. When the cells grow to 80%, the HEK 293T cell group is co-transfected with 10ng pCoV-Gluc, 200ng eukaryotic codon-optimized plasmid pCOVID19-nsp12, 600ng eukaryotic codon-optimized plasmid pCOVID19-nsp7 and 600ng eukaryotic codon-gluc per well Suboptimized plasmid pCOVID19-nsp8 plasmid. 4 hours after transfection, the medium was replaced with DMEM medium containing 10% fetal bovine serum (FBS), and 2 μL of 5-iodotubercidin at 5.00 mM or 10.00...

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Abstract

The invention discloses an application of an adenosine kinase inhibitor in preparation of an anti-coronavirus preparation. The adenosine kinase inhibitor is 5-iodo tubercle bacillus. It is found for the first time that 5-iodo tubercle bacillus can obviously inhibit the activity of coronavirus-dependent RNA polymerase and shows good resistance to SARS-CoV-2 excision enzyme, and then application of 5-iodo tubercle bacillus in preparation of a coronavirus-dependent RNA polymerase antagonist and anti-coronavirus drugs is provided. The invention provides a small molecule compound capable of effectively resisting the coronavirus, so that the treatment means of the coronavirus is further enriched.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of adenosine kinase inhibitors in the preparation of anti-coronavirus preparations. Background technique [0002] Novel coronavirus disease 2019 (COVID-19) is a serious threat to human health and is caused by a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). The discovery of new drugs against 2019-nCoV is an important part of prevention and control measures, and the discovery of new drugs will provide an important treatment plan for the clinical prevention and treatment of 2019-nCoV. [0003] Gene sequencing results show that SARS-CoV-2, like SARS-CoV and MERS-CoV, belongs to the genus of coronavirus β, and its gene sequence homology with SARS-CoV is 75%-80%, and it is similar to bat SARS-like coronavirus. The homology of (bat-sl-coVZC45) exceeds 85%. Compared with SARS-CoV virus, SARS-CoV-2 virus has stronger infectivity, an...

Claims

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Application Information

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IPC IPC(8): A61K31/7064A61P31/14
CPCA61K31/7064A61P31/14Y02A50/30
Inventor 岑山赵建元李晓宇张永欣
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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