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Application of salvia miltiorrhiza extract and quinone compounds in resisting coronavirus

A coronavirus and virus technology, applied in the direction of antiviral agents, medical preparations containing active ingredients, organic active ingredients, etc., to achieve the effects of low cytotoxicity, easy oral administration, and low toxic and side effects

Pending Publication Date: 2021-11-23
SHANGHAI TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0039] In the prior art, none of the above drugs can be used to treat related diseases caused by coronavirus

Method used

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  • Application of salvia miltiorrhiza extract and quinone compounds in resisting coronavirus
  • Application of salvia miltiorrhiza extract and quinone compounds in resisting coronavirus
  • Application of salvia miltiorrhiza extract and quinone compounds in resisting coronavirus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0125] Example 1 Through multiple in vitro enzyme activity experiments, it was found that 10 compounds such as tanshinone I can significantly inhibit the papain-like protease activity of the new coronavirus (SARS-CoV-2)

[0126] In vitro enzyme activity test conditions are as follows:

[0127] Fluorescent substrate for enzyme activity experiment: Z-Arg-Leu-Arg-Gly-Gly-AMC (from Jill Biochemical), the excitation wavelength and emission wavelength of this fluorescent substrate are 340nm and 460nm, respectively.

[0128] The enzyme activity reaction buffer used in the experimental procedure is 50mM HEPES, pH 7.5, 0.1mg / ml BSA, 2mMDTT; enzyme activity reaction temperature: 30°C.

[0129] The specific experimental steps are as follows: at the beginning of the reaction, add papain-like protease, the final concentration of papain-like protease is 0.2 μM, and 50 μM inhibitors (10 kinds of small molecule compounds: tanshinone I, tanshinone IIA sulfonic acid, β-lapachone, Cryptotanshin...

Embodiment 2

[0132] Through multiple in vitro enzyme activity experiments, it was found that tanshinone I and cryptotanshinone could significantly inhibit the papain-like protease activity of the new coronavirus (SARS-CoV-2) ( Figure 11 and 13 ).

[0133] The in vitro enzyme activity test steps are: SARS-CoV-2 papain-like protease at a final concentration of 200nM (refer to Zhao Y, DuX, Duan Y, et al. High-throughput screening identifies established drugs asSARS-CoV-2PLpro inhibitors[J].Protein&Cell , 2021:1-12.), inhibitor solutions with different concentration gradients and 20 μM fluorescent substrate (Arg-Leu-Arg-Gly-Gly-AMC) were added in a 60 μl reaction system (50mM HEPES, pH=7.5, 0.1mg ml-1BSA), incubate at room temperature for 10 min, use emission light 340nm and excitation light 460nm to detect the initial reaction rate of the fluorescent substrate, and obtain the inhibition rate curve by comparing the initial rate with the control group without drug addition. The experiment wa...

Embodiment 3

[0136] Through in vitro cell virus experiments, it was found that tanshinone I and cryptotanshinone can significantly inhibit the replication ability of SARS-CoV-2 in cells, and the cytotoxicity is low. EC 50 The values ​​are 2.26 μM and 0.7 μM, respectively. CC 50 The values ​​are all greater than 300 μM. For specific results, see Figure 12 and Figure 14 .

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Abstract

The invention discloses an application of a salvia miltiorrhiza extract and quinone compounds in resisting coronavirus. One or more compounds of tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone I, beta-lapamoquinone, L-shikonin, 2-methoxy-1, 4-naphthoquinone, CPI-169, S3I-201 and plumbagin, pharmaceutically acceptable salts thereof, solvates thereof, solvates of the pharmaceutically acceptable salts thereof, or crystal forms thereof are applied in preparation of anti-coronavirus agents, medicines for treating and / or preventing diseases caused by coronavirus, and / or an inhibitor for inhibiting papaya-like protease. The compounds can well inhibit the activity of the papaya-like protease in the coronavirus and inhibit the replication ability of the coronavirus in cells so as to inhibit the activity of the coronavirus, and when the compounds are used for treating diseases caused by the coronavirus, the toxic and side effects are low, and oral administration is easy to implement.

Description

technical field [0001] The present invention relates to the technical field of biomedicine, in particular to the application of salvia miltiorrhiza extract and quinone compounds in anti-coronavirus, in particular to the application of tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone I, β-lapachone, Compounds of one or more of levoshikonin, 2-methoxy-1,4-naphthoquinone, CPI-169, S3I-201 and plumbagin, their pharmaceutically acceptable salts, and their solvates substances, solvates of their pharmaceutically acceptable salts, or crystal forms thereof are used in the preparation of anti-coronavirus agents, in the preparation of drugs for the treatment and / or prevention of diseases caused by coronaviruses, and / or in the preparation of drugs that inhibit papain-like protease application of inhibitors. Background technique [0002] Coronaviruses are a class of viruses that are closely related to humans and animals. Coronaviruses HCoV-229E and HCoV-OC43 cause the ...

Claims

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Application Information

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IPC IPC(8): A61K31/58A61K31/352A61K31/122A61K31/4439A61K31/192A61P31/14
CPCA61K31/58A61K31/352A61K31/122A61K31/4439A61K31/192A61P31/14A61K2300/00
Inventor 杨海涛靳振明杜小宇段胤凯赵耀杨秀娜饶子和
Owner SHANGHAI TECH UNIV
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