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Application of harringtonine in preparation of medicine for resisting novel coronavirus

A technology of harringtonine and antiviral drug, which is applied in the field of antiviral drug preparation and achieves significant anti-SARS-CoV-2 effect

Active Publication Date: 2022-03-15
XI AN JIAOTONG UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, there are gaps in current research on the use of harringtonine as an anti-SARS-CoV-2 pneumonia drug

Method used

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  • Application of harringtonine in preparation of medicine for resisting novel coronavirus
  • Application of harringtonine in preparation of medicine for resisting novel coronavirus
  • Application of harringtonine in preparation of medicine for resisting novel coronavirus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1 3

[0030] Example 1 Harringtonine specifically binds to the S protein of SARS-CoV-2 and the cell TMPRSS2 protein

[0031] CMC is a kind of affinity chromatography, which uses the cell membrane with specific receptor overexpression as the stationary phase, which can realize high-throughput screening of components that specifically bind to membrane receptors under biomimetic conditions, and is a reliable means for screening active ingredients of traditional Chinese medicine. The S protein of SARS-CoV-2 and HEK293T cells with high expression of cell TMPRSS2 enzyme were used to prepare cell membranes, which were adsorbed with activated silica gel to prepare cell membrane chromatography stationary phases, and SARS-CoV-2-S were obtained after wet packing. h / CMC column and TMPRSS2 h / CMC chromatographic column for HPLC detection, and HEK293T / CMC is the CMC control for protein specific binding. The results are shown in Table 1:

[0032] Table 1 Retention time of harringtonine on vario...

Embodiment 2 3

[0035] Example 2 Harringtonine inhibits cell membrane fusion induced by binding of S protein to ACE2

[0036] ACE2 high-expressing cells were seeded in 96-well plates, and each well was supplemented with medium to 50 μL. Incubate for 2 hours in a 37°C, 5% CO2 incubator to adhere to the wall. Add harringtonine prepared in culture medium at a concentration of 0, 0.625, 1.25, 2.5, 5, and 10 μM, and add 50 μL of HEK293T cells highly expressing S protein and green fluorescent protein (GFP), and continue to infect for 8 hours. , for fluorescence microscopy observations. It can be seen that the cells with high expression of ACE2 in the non-administration group and the HEK293T cells with high expression of S protein and GFP undergo membrane fusion to form syncytia of multiple cells. When the drug concentration of harringtonine in the administration group reached 1 μM, the number of syncytia was significantly reduced, and the boundaries between individual cells were clear. It shows ...

Embodiment 3 3

[0037] Example 3 Harringtonine inhibits SARS-CoV-2 pseudovirus from infecting ACE2 high-expressing cells

[0038] ACE2 high-expressing cells were seeded in 96-well plates, and each well was supplemented with medium to 50 μL. 37°C, 5% CO 2 Incubate in the incubator for 2 hours to adhere to the wall. Add different concentrations of harringtonine prepared in culture medium, add 5 μL SARS-CoV-2 pseudovirus to each well and infect for 4 hours, make up to 100 μL culture volume, continue to infect for 6-8 hours, replace with 200 μL new complete culture Then continue to culture at 37°C for 48h. The Luciferase Assay System kit detects the luminescence value of Luciferase. See Table 2 for the results:

[0039] Table 2 Harringtonine inhibits SARS-CoV-2 pseudovirus from infecting ACE2 high-expressing cells

[0040]

[0041] As can be seen from Table 2, harringtonine has inhibitory effect on the infectivity of SARS-CoV-2 pseudovirus in a dose-dependent manner, and its IC 50 is 0.78±...

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Abstract

The invention discloses application of harringtonine to preparation of a novel coronavirus resisting medicine, and belongs to the technical field of antiviral medicine preparation, the medicine is analyzed through an SARS-CoV-2-Sh / CMC model and a TMPRSS2h / CMC model, and the binding specificity of the harringtonine and SARS-CoV-2 S protein and cell TMPRSS2 enzyme is determined; the SARS-CoV-2 pseudovirus is utilized to infect ACE2 high-expression cells and ACE2 / TMPRSS2 common high-expression cells, and it is proved that the drug has the characteristic of double targets; a Vero E6 cell is infected by using an SARS-CoV-2 original strain and a Delta 630 mutant strain, and it is proved that the medicine has a remarkable SARS-CoV-2 resisting effect and is more sensitive to the inhibiting effect of the Delta 630 mutant strain.

Description

technical field [0001] The invention belongs to the technical field of preparation of antiviral drugs, in particular to the application of harringtonine in the preparation of anti-new coronavirus drugs. Background technique [0002] The clinical classification of the disease caused by the new coronavirus (SARS-CoV-2) is mild, common, severe and critical. The main manifestations are fever, dry cough, fatigue, etc., and a small number of patients are accompanied by nasal congestion, runny nose, diarrhea, etc. Upper respiratory tract and gastrointestinal symptoms, high clinical fatality rate and poor prognosis. The first step of SARS-CoV-2 invading host cells is "membrane fusion". After lysis, the process of invading the host cell is initiated. [0003] The new coronavirus variant B.1.1529 is mainly due to the emergence of more than 30 mutation points on the virus S protein, including 10 mutation points in the receptor binding region RBD. The mutant strain of the new coronav...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/55A61K36/13A61P31/14
CPCA61K31/55A61K36/13A61P31/14Y02A50/30
Inventor 贺浪冲王楠张化俊贺怀贞王程胡时灵卢闻张涛马维娜
Owner XI AN JIAOTONG UNIV
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