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Application of Ebselen in preparation of coronavirus papaya-like protease inhibitor and anti-coronavirus infection medicine

A technology for protease inhibitors and coronaviruses, applied in antiviral agents, active ingredients of heterocyclic compounds, etc., can solve the problems of lack of effective prevention and treatment drugs

Pending Publication Date: 2022-05-13
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Aiming at the lack of effective prevention and treatment drugs for related inflammatory diseases such as lung, respiratory and intestinal diseases, nervous system symptoms and myocarditis caused by coronavirus, the present invention proposes Ebselen and its pharmaceutical Application of acceptable salts in the preparation of coronavirus papain-like protease inhibitor drugs

Method used

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  • Application of Ebselen in preparation of coronavirus papaya-like protease inhibitor and anti-coronavirus infection medicine
  • Application of Ebselen in preparation of coronavirus papaya-like protease inhibitor and anti-coronavirus infection medicine
  • Application of Ebselen in preparation of coronavirus papaya-like protease inhibitor and anti-coronavirus infection medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: The fluorescence intensity of the substrate peptide under the action of different concentrations of Ebselen under the metabolism of papain-like protease changes with time

[0038] The specific implementation process is:

[0039] (1) The stock solutions of SARS-CoV-2 papain-like protease and substrate peptide were stored in a -80°C refrigerator;

[0040] (2) Thaw SARS-CoV-2 papain-like protease in a freezing plate (-4 to 4°C) at room temperature, take 1uL and dilute it in 98uL borate borax buffer (PH=7.4), and add it to the detection plate;

[0041] (3) Add 1uL of different concentrations of Ebselen, 0, 0.025mM, 0.125mM, 0.25mM, 0.5mM, 1mM, 2.5mM, into the solution obtained in the above step (2);

[0042] (4) Add 1uL of the same concentration of substrate peptide (0.5mM) to the solution obtained in the above step (3), incubate at 37°C with a fluorescent microplate reader, and use a fluorescent microplate reader to monitor excitation at 342nm and fluorescence ...

Embodiment 2

[0044] Example 2: Detection of the inhibitory ability of Ebselen to novel coronavirus papain-like protease

[0045] The specific implementation process is as follows:

[0046] (1) The stock solutions of SARS-CoV-2 papain-like protease and substrate peptide were stored in a -80°C refrigerator;

[0047] (2) Thaw SARS-CoV-2 papain-like protease in a freezing plate (-4 to 4°C) at room temperature, take 1uL and dilute it in 98uL borate borax buffer (PH=7.4), and add it to the detection plate;

[0048] (3) Add 1 uL of different concentrations of inhibitors (Ebselen concentrations are 0, 0.025mM, 0.125mM, 0.25mM, 0.5mM, 1mM, 2.5mM) to the solution obtained in the above step (2);

[0049] (4) Add 1uL of the same concentration of substrate peptide (0.5mM) to the solution obtained in the above step (3), incubate at 37°C with a fluorescent microplate reader, and use a fluorescent microplate reader to monitor excitation at 342nm and fluorescence emission at 496nm Value, detect while inc...

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Abstract

The invention relates to the technical field of medicinal chemistry, in particular to application of Ebselen in preparation of a coronavirus papaya-like protease inhibitor and a medicine. The application of the Ebselen or the pharmaceutically acceptable salt thereof in at least one of the following aspects: the application in preparation of a coronavirus papaya-like protease inhibitor; the invention also relates to an application in preparation of a medicament for resisting coronavirus infection. The invention relates to application in preparation of products for inhibiting coronavirus. In the technical scheme provided by the invention, Ebseen has an inhibition effect on the enzymatic activity of target papaya-like protease of coronavirus, especially has a relatively strong inhibition effect on the enzymatic activity of target papaya-like protease of new coronavirus, and has the potential of being developed into drugs for treating and preventing coronavirus, especially resisting new coronavirus.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to the application of Ebselene in the preparation of coronavirus papain-like protease inhibitors and medicines. Background technique [0002] Coronaviruses are a large family of viruses with the largest genome among currently known positive-strand RNA viruses. According to the host, serotype gene sequence and structure, coronaviruses can be divided into four categories: α, β, γ and δ. Among these four types, α and β can only infect mammals, and γ and δ mainly infect birds; α coronaviruses include human coronaviruses (HCoV-229E, HCoV-NL63), long-winged bat coronaviruses (HKU1 , HKU8), canine coronavirus (CCoV) and feline coronavirus (FCoV), etc.; Virus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Mouse Coronavirus, Fruit Bat Coronavirus HKU9, etc.; γ-type coronaviruses mainly include avian coronaviruses such as Chicken Infectious Bronchitis Virus...

Claims

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Application Information

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IPC IPC(8): A61K31/41A61P31/14
CPCA61K31/41A61P31/14
Inventor 韩克利王艺颖贾燕张洪苓
Owner SHANDONG UNIV
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