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Application of gallic acid as well as derivatives and structural analogues thereof in preparation of anti-coronavirus drugs

A technology similar to gallic acid and structure, applied in the field of biomedicine, can solve problems such as discounted antiviral effects of chemical drugs, weakness, and potential safety hazards

Inactive Publication Date: 2020-09-15
GUANGZHOU SHENGPU INVESTMENT MANAGEMENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, the above-mentioned drugs are prone to adverse reactions such as diarrhea, anemia, dizziness, headache, and weakness, and there are certain safety hazards; and with the mutation of the virus and the emergence of new strains, the antiviral effect of these chemical drugs is greatly reduced. For example, at the end of 2019 Novel coronavirus 2019-nCoV has emerged, and no effective drug has been found so far

Method used

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  • Application of gallic acid as well as derivatives and structural analogues thereof in preparation of anti-coronavirus drugs
  • Application of gallic acid as well as derivatives and structural analogues thereof in preparation of anti-coronavirus drugs
  • Application of gallic acid as well as derivatives and structural analogues thereof in preparation of anti-coronavirus drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Example 1 Cell half infection dose (TCID 50 ) determination

[0065] 1. Experimental materials

[0066] Virus: 2019-nCoV; cell line: human embryonic kidney cell 293 (HEK293 cells); DMEM medium; 96-well culture plate.

[0067] 2. Experimental steps

[0068] (1) In a centrifuge tube, the virus is diluted 10 times continuously with DMEM medium, starting from 10 -1 to 10 -6 , incubate on ice for 1-2 hours;

[0069] (2) Add virus solutions of different concentrations in a 96-well culture plate, inoculate a vertical row for each dilution, a total of 8 wells, inoculate 100 μl in each well, and add virus-free DMEM medium into two rows as a normal control;

[0070] (3) Digest, suspend, and count cultured human embryonic kidney cells 293 (HEK293 cells), add 100 μl of cell suspension to each well of a virus-containing 96-well plate, and make the cell density 2 to 3×10 5 a / mL;

[0071] (4) 37°C, 5% CO 2 Cultivate in the incubator, observe the cytopathic effect (CPE), until ...

Embodiment 2

[0075] Effect of Example 2 on the activity of HEK293 cells infected by 2019-nCoV virus

[0076] 1. Experimental materials:

[0077] (1) Drugs: See Table 1 for the compounds.

[0078] (2) Other experimental materials

[0079] The virus is 2019-nCoV; the cell line is human embryonic kidney cell 293 (HEK293 cells); DMEM medium; 96-well culture plate.

[0080] 2. Experimental steps

[0081] (1) Take the cell culture solution and dilute the drug into a series of mass concentrations (100, 33.33, 11.11, 3.70, 1.23, 0.41 and 0.00 mg / mL);

[0082] (2) Take another 50TCID 50 The 2019-nCoV virus liquid is neutralized with the above drug solution in equal volume;

[0083](3) After incubating at 37°C for 1 hour, inoculate in HEK293 cells, 100 μL / well, 4 replicate wells for each mass concentration, and set normal cell control group, virus control group and positive control group at the same time, 37°C, 5% CO 2 Cultivate and observe cell morphology;

[0084] (4) After 48 hours, use th...

Embodiment 3

[0090] Embodiment 3 is to the impact of SARS-CoV virus infection HEK293 cell activity

[0091] 1. Experimental materials:

[0092] (1) Drugs: See Table 1 for the compounds.

[0093] (2) Other experimental materials

[0094] The virus is SARS-CoV; the cell line is human embryonic kidney cell 293 (HEK293 cells); DMEM medium; 96-well culture plate.

[0095] 2. Experimental procedure: refer to Example 2.

[0096] 3. Experimental results:

[0097] As shown in Table 3, compounds 1-45 all showed high antiviral activity, and their EC 50 Values ​​range from 3 to 18 μg / ml.

[0098] The EC of table 3 compound on human embryonic kidney cell 293 (HEK293 cell) line that has been infected with SARS-CoV virus 50 value

[0099]

[0100]

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Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of gallic acid as well as derivatives and structural analogues thereof in preparation of anti-coronavirus drugs. Researches show that gallic acid as well as derivatives and structural analogues thereof have an obvious antivirus effect on coronaviridae viruses including 2019 novel coronaviruses (2019-nCoV or SARS-CoV-2), Middle East respiratory syndrome coronaviruses (MERS-CoV) and the like. Gallic acid substances are natural, widely exist in various plants, are polyphenol compounds existing in the nature, are widely applied to the fields of food, biology and medicine, and are very safe, so that the substances have very good application value in the aspect of preparation and development of antiviral drugs for coronaviridae.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to the application of gallic acid and its derivatives and structural analogs in the preparation of anti-coronavirus drugs. Background technique [0002] In terms of systematic classification, coronaviruses belong to the order Nidovirales, the family Coronaviridae, and the genus Coronavirus. Among them, the viruses of the coronavirus genus are RNA viruses with an envelope and a linear single-stranded positive strand genome, and are a large class of viruses that exist widely in nature. The diameter of coronavirus is about 80-120nm, the 5′ end of the genome has a methylated cap structure, and the 3′ end has a poly(A) tail. The total length of the genome is about 27-32kb. . Coronaviruses only infect vertebrates, including humans. Currently, coronaviruses known to infect humans and cause severe outbreaks include SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-229E, HCoV-NL63,...

Claims

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Application Information

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IPC IPC(8): A61K31/192A61K31/366A61K31/353A61K31/7024A61K31/7048A61K31/235A61K31/7012A61P31/14
CPCA61K31/7012A61K31/7048A61P31/14A61K2300/00
Inventor 付军
Owner GUANGZHOU SHENGPU INVESTMENT MANAGEMENT
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