Application of proanthocyanidins in the preparation of anti-Zika virus drugs

A Zika virus and proanthocyanidin technology, which can be used in antiviral agents, resistance to vector-borne diseases, pharmaceutical formulations, etc., can solve the problem that other compounds have no anti-Zika virus activity, and achieve good medicinal prospects and antiviral activity. Strong and safe effect

Active Publication Date: 2021-02-05
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, except for (-)-epigallocatechin gallate (-)-Epigallocatechin gallate, no other compounds have been reported on anti-Zika virus activity

Method used

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  • Application of proanthocyanidins in the preparation of anti-Zika virus drugs
  • Application of proanthocyanidins in the preparation of anti-Zika virus drugs
  • Application of proanthocyanidins in the preparation of anti-Zika virus drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1: Anti-Zika virus activity test based on Q-PCR

[0041] 1. Experimental materials

[0042] (1) Cell line: African green monkey kidney cells (vero cell line) donated by Jin Xia's research group

[0043] (2) Virus strain: Zika virus strain (Microbial Virus Collection Center, Wuhan Institute of Virology, Chinese Academy of Sciences)

[0044] (3) Main reagents: TRNzol lysate (Tiangen), chloroform, isopropanol, 75% ethanol, reverse transcription kit (ReverTraAce qPCR RT, Yoyobo), real-time fluorescent quantitative PCR kit (SYBR Green Realtime PCRMasterMix, Toyobo, Japan)

[0045] (4) Main instruments: Eppendorfcentrifuge 5424R cryogenic centrifuge, Applied Biosysytems PCR instrument, Applied Biosysytems quantistudio 6Flex, Haier refrigerator

[0046] 2. Experimental method

[0047] (1) Compounds and Zika virus co-treated African green monkey kidney cells

[0048] 4μL 1×10 6 16 compounds (see figure 1 listed) mix well and process 4×10 at the same time 4 Afric...

Embodiment 2

[0066] Embodiment two: IC of 5 kinds of compounds with antiviral activity 50 calculate

[0067] 1. Experimental materials

[0068] (1) Main reagents: the same as in Example 1.

[0069] (2) main instrument: with embodiment one.

[0070] 2. Experimental method

[0071] (1) Five compounds screened out in Example 1 and Zika virus were simultaneously treated with African green monkey kidney cells

[0072] 1) 4μL 1×10 6 Zika virus (MOI=0.1) was mixed with five compounds of different doses (0, 0.5, 1, 2, 4, 8, 16, 32, 64 μ M) (see image 3 listed) mix well and process 4×10 at the same time 4 African green monkey kidney cells, the supernatant was discarded after 48 hours, and the cells were harvested.

[0073] (2) Intracellular RNA extraction and reverse transcription, real-time quantitative Q-PCR.

[0074] Concrete method is the same as embodiment one.

[0075] 3. Experimental results

[0076] The results were calculated by Graphpad software, the IC of 5 compounds including...

Embodiment 3

[0077] Embodiment 3: Cytotoxicity experiment

[0078] 1. Experimental materials

[0079] (1) Main reagent: CellTiter-Glo reagent (Promega)

[0080] (2) Main instrument: multifunctional microplate reader (Thermo)

[0081] 2. Experimental method

[0082] (1) 2×10 cells spread in 96-well plate 4 Vero cells were treated with five compounds at different concentrations (0, 0.5, 1, 2, 4, 8, 16, 32, 64 μM) for 2 days, and the cell viability was detected using CellTiter-Glo reagent (Promega): Add 100 μL of CellTiter-Glo detection reagent to each cell culture well, place it on a shaker at room temperature for 20 minutes, and use a white microwell luminescence quantifier to detect the fluorescence value.

[0083] 3. Experimental results

[0084] Such as Figure 4 Shown: except the compound NSF245 which has obvious cytotoxicity at a higher dose, the other three compounds have no obvious cytotoxicity.

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Abstract

The invention provides application of proanthocyanidin compounds shown by the formula (I) as shown in the specification or a pharmaceutically acceptable salt thereof to preparation of a drug against Zika virus, and provides the novel application of the proanthocyanidin compounds shown by the formula (I) in the specification or the pharmaceutically acceptable salt thereof in the pharmaceutical field. The compounds can effectively inhibit the expansion of Zika virus, and can be used as a lead compound to develop the drug for preventing and treating Zika virus infection. Active compounds have nosignificant cytotoxicity at the inhibitor dose and have a common parent nucleus structure, but the parent nucleus structure has no antiviral activity, wherein, the active compounds, namely proanthocyanidins, are found to have anti-Zika virus activity in African green monkey kidney cells and human glioma cells. The compounds have important application prospects.

Description

technical field [0001] The present invention relates to the field of pharmaceutical application inventions, in particular to the application of proanthocyanidin compounds in the preparation of anti-Zika virus medicines. Background technique [0002] Zika virus (ZikaVirus, ZIKV) is a single-stranded, non-segmented, positive-strand RNA virus, an arbovirus transmitted by mosquitoes, belonging to the family Flaviviridae, the genus Flavivirus, and Flaviviruses such as Dengue Virus, Yellow Fever Virus, Japanese Encephalitis Virus, and West Nile Virus are closely related and highly infectious. In 2015, Zika outbreaks were reported in Central and South America (Brazil and Colombia) and Africa (Cape Verde). Subsequently, more than 13 American countries reported Zika virus infection, and many countries in Europe, Asia, and Oceania also found imported cases. According to preliminary estimates from the Brazilian health department, there were about 440,000 to 1.3 million Zika virus inf...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/353A61P31/14
CPCA61K31/353Y02A50/30
Inventor 朱维良钟劲施一徐咏芬徐志建朱正诞郭明哲宋豪段文倩邵强叶丽清
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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