CN113116872B - Application of pterostilbene in anti-influenza A virus medicine - Google Patents
Application of pterostilbene in anti-influenza A virus medicine Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
Abstract
The invention belongs to the technical field of anti-influenza virus application, and particularly relates to application of pterostilbene in an anti-influenza A virus medicament. The monomer pterostilbene targets an influenza virus non-structural protein NS1, inhibits activation of a host PI3K/Akt signal pathway, plays an antiviral role, and can be used for preparing a medicament for preventing and treating influenza; the monomer pterostilbene can be used as a lead compound for structural modification, so that a compound with better activity is obtained and an anti-influenza virus medicine is prepared. The pterostilbene is used as a natural monomer, provides a new micromolecule natural medicine for preventing and treating the influenza virus diseases, can inhibit influenza A virus from infecting host cells, thus providing a new way and means for preventing and treating the influenza virus diseases, and has important research and development values and development significance.
Description
Technical Field
The invention belongs to the technical field of anti-influenza virus application, and particularly relates to application of pterostilbene in an anti-influenza A virus medicament.
Background
Influenza (influenza for short) is a respiratory infectious disease caused by influenza virus, has the characteristics of high morbidity, wide epidemic, rapid transmission and the like, and causes serious threat and burden to social health and economy, and according to the statistics of the world health organization, seasonal influenza per year can cause about 300 to 500 ten thousand severe cases and 30 to 50 ten thousand cases to die.
The vaccination is the main line of defense and the most effective way for preventing the infection of the influenza virus, and because the antigenicity of the influenza A virus is easy to be changed, the autoimmune memory formed in the organism is ineffective, therefore, a new vaccine needs to be developed and vaccinated according to the epidemic virus strain of the year every year, and the preventive effect of the vaccine is greatly limited. The use of antiviral drugs is the primary route to treat influenza. Two types of antiviral drugs currently used clinically are mainly targeted influenza virus proteins, namely M2 ion channel inhibitors (such as adamantane drugs) and neuraminidase inhibitors (such as zanamivir, oseltamivir and peramivir), respectively. The former can only inhibit influenza A virus, is not effective on influenza B virus, and has been applied clinically for years, which leads to general drug resistance, so that the alkylamine drug is no longer selected for clinically treating influenza. The latter is effective against influenza a and b viruses, and has been widely used before 2008, and at present, an oseltamivir-resistant virus strain H1N1pdm09 has been detected, and zanamivir resistance is increasing due to wide abuse. Therefore, there is an urgent need for new influenza therapeutic drugs with new mechanisms of action to address the continuing threat against influenza viruses.
In recent years, Chinese medicines play an important role in treating influenza (such as H5N1 and H7N 9), SARS and virus infectious diseases such as novel coronavirus which are epidemic at present, the role of Chinese medicines in virus infection is highly concerned by experts and scholars at home and abroad, and influenza virus infection belongs to the fields of pestilence, warm disease and the like in the traditional Chinese medicine and is caused by the affection of untimely qi or pathogenic factors of pestilence, exopathic muscle striae and internal accumulation in lung and stomach. During the period of the COVID-19 epidemic, the application of the traditional Chinese medicine and the good treatment effect thereof push the application of the traditional Chinese medicine to the hot spot for treating the virus infectious diseases again, and people are increasingly interested in searching the medicines or lead compounds for treating the serious diseases from plants. Therefore, the development of novel anti-influenza drugs is urgently needed in clinic.
Disclosure of Invention
In view of the above problems, the present invention aims to provide an application of pterostilbene in an anti-influenza a virus drug, wherein pterostilbene is used as a natural monomer, which can inhibit influenza a virus from infecting host cells, thereby providing a new way and means for preventing and treating influenza a virus diseases.
The technical content of the invention is as follows:
the invention provides application of pterostilbene in an anti-influenza A virus medicament.
The monomer pterostilbene targets an influenza virus non-structural protein NS1, inhibits activation of a host PI3K/Akt signal pathway, plays an antiviral role, and can be used for preparing a medicament for preventing and treating influenza;
the monomer pterostilbene can be used as a lead compound for carrying out structural modification to obtain a compound with better activity and prepare an anti-influenza virus medicament;
the application of the monomer pterostilbene in preparing the anti-influenza A medicament can prepare the compound into injection, tablets, powder, granules, capsules and oral liquid by combining the modern common pharmaceutical preparation means, thereby adopting a more convenient oral administration form.
The medicaments in various dosage forms can be prepared according to the conventional method in the pharmaceutical field.
Pterocarpus santalinus, also known as: pterocarpus marsupium, Rosa multiflora, Pterocarpus marsupium, Dracocephalum heterophyllum, and Cupressus buergeriana. The distribution is in Guangdong, Yunnan and the like; collected in summer and autumn. The efficacy of red sandalwood has been discovered for a long time in China and is applied to ancient medicine. According to the records in the ancient literature, "Ben Cao Jing Shu": zizhen sandalwood is used for treating toxic wind. So it is easy to generate toxicity when it is generated by heat and even wind, nutrient and blood are injured. The herb can enter blood when salty in property, and can clear heat when cold in property, so it is toxic and self-eliminating . Take the herb for spreading jin Jiang, stopping bleeding and alleviating pain when carrying the herb in sight. It should be combined with Fangjiang Xiang to make into very fine powder for treating sore. The modern medical research finds that the rosewood has the effects of resisting cancer and oxidation, treating androgenetic alopecia of rats, diminishing swelling, resisting inflammation and the like; through pharmacological component analysis, the pterocarpus santalinus contains active ingredients such as pterocarpin, homopterocarpin, pterocarpus santalinus, deoxypterocarpus santalinus, pterostilbene and pterocarpan. Pterostilbene (Pterostilbene), also known as 3, 5-dimethoxy-4' -hydroxystilbene (as shown in figure 1), was the first name found in pterocarpus indicus and widely exists in berries such as blueberry, grape and the like. A large number of researches prove that the pterostilbene has the effects of resisting oxidation, inflammation and aging, regulating blood fat, protecting liver and kidney and the like; meanwhile, the composition has the effects of preventing and treating metabolic diseases, cardiovascular diseases, cancers and the like.
The invention has the following beneficial effects:
the pterostilbene is used as a natural monomer and can inhibit influenza A virus from infecting host cells, so that a new way and means are provided for preventing and treating influenza virus diseases, and the pterostilbene has important research and development values and development significance;
the invention discovers that the pterostilbene has the function of resisting influenza A virus for the first time, and provides a new micromolecule natural medicine for preventing and treating influenza virus diseases;
the pterostilbene has no cytotoxicity in a concentration range, and can be used for preparing a medicament for preventing and treating influenza;
the pterostilbene can be used as a lead compound for carrying out structural modification;
the pterostilbene anti-influenza A virus disclosed by the invention has an action mechanism of targeting an influenza virus NS1 protein, inhibiting the interaction of an NS1 protein and a host PI3K/Akt signal channel, inhibiting virus replication, and can be used for preparing a medicine for preventing and treating influenza.
Drawings
FIG. 1 is a chemical structural formula of pterostilbene;
FIG. 2 is a graph showing the results of the cytotoxicity test using pterostilbene;
FIG. 3 is a graph of the results of the assay of pterostilbene for inhibiting the expression of influenza virus proteins;
FIG. 4 is a graph of the results of a test for pterostilbene in inhibiting replication of influenza virus progeny;
FIG. 5 is a graph of the results of the assay of pterostilbene for inhibiting the expression of influenza virus genes;
FIG. 6 is a graph showing the results of the inhibition of the expression of NP protein of influenza virus by pterostilbene;
FIG. 7 is a graph showing the results of using time point dosing experiments to detect pterostilbene acting on the later stage of virus replication;
FIG. 8 is a graph showing the results of an experiment on the binding between pterostilbene and NS1 protein;
FIG. 9 is a graph of PI3K/Akt signaling pathway activation following inhibition of influenza infection by pterostilbene.
Detailed Description
The present invention is described in further detail in the following description of specific embodiments and the accompanying drawings, it is to be understood that these embodiments are merely illustrative of the present invention and are not intended to limit the scope of the invention, which is defined by the appended claims, and modifications thereof by those skilled in the art after reading this disclosure that are equivalent to the above described embodiments.
All the raw materials and reagents of the invention are conventional market raw materials and reagents unless otherwise specified.
Preparing materials:
human lung epithelial cells a549 were cultured in RPMI1640 medium containing 10% heat-inactivated Fetal Bovine Serum (FBS), 50 units ml of penicillin and 50 μ g/ml of streptomycin (P/S);
canine kidney cells (MDCK) were cultured in DMEM medium containing 10% heat-inactivated Fetal Bovine Serum (FBS), 50 units ml of penicillin, and 50 μ g/ml of streptomycin (P/S);
influenza virus Influenza A/WSN/1933 was amplified in 9-day chick embryos and stored at-80 ℃.
All virus-related experiments were performed in a biosafety level 2 facility.
Example 1
Pterostilbene was used for respiratory epithelial cells and toxicity assessment:
a549 cells at 1 × 104Perwell in 96-well plates, 5% CO at 37 ℃2Culturing in an incubator overnight;
discarding supernatant of cells, and adding pterostilbene diluted by multiple times into lung epithelial cells (A549);
the MTT method is used for detecting the cytotoxicity of pterostilbene on respiratory epithelial cells: after 48 hours, the supernatant was discarded, and a medium containing 0.5 mg/ml MTT was added to each well, incubated at 37 ℃ for 4 hours, and then the absorbance at OD570 nm was measured by a microplate reader.
As shown in fig. 2, the experimental results showed that pterostilbene was less toxic to a549 cells, and at a maximum concentration of 200 μ M, cell survival was > 75%.
Example 2
The pterostilbene is used for evaluating the respiratory epithelial cells and the capability of inhibiting virus infection:
1) a549 cells at 3X 105Perwell in 6-well plates, 5% CO at 37 ℃2Culturing in an incubator overnight;
2) discarding the supernatant of the cells, diluting the virus with serum-free RPMI1640 medium, inoculating A549 cells with a virus titer of MOI =1, and adsorbing for 1h at 37 ℃ in A5% CO2 incubator;
3) after virus infection, virus supernatant was discarded, pterostilbene diluted by multiples of RPMI1640 without serum was added to the cells at 37 ℃ with 5% CO2Continuously culturing in an incubator;
4) after 24 hours, a) collecting cell proteins, and detecting the expression of influenza virus-associated proteins NP, M2 and PB2 by using western blot, wherein the result is shown in figure 3; compared with the virus control group, after the pterostilbene is added into the cells for treatment, the expression levels of the influenza virus proteins NP, PB2 and M2 are lower than those of the control group.
b) Cell supernatants were collected and the titer of progeny virus in maintenance fluid was determined by plaque assay, the results are shown in FIG. 4: compared with a virus infection control group, the pterostilbene can effectively inhibit the titer of progeny viruses in influenza virus infected cells, and the inhibition effect is concentration-dependent.
c) Extracting cell RNA, detecting the expression of influenza virus related genes by adopting Real-time PCR, and obtaining a result shown in figure 5; 20 mu M pterostilbene can effectively inhibit the expression of mRNA of NP and PB2 genes of influenza viruses in A549 cells.
The pterostilbene can obviously inhibit the expression of influenza virus NP, M2 and PB2 proteins, inhibit the generation of progeny viruses, inhibit the expression of virus genes and show an effective anti-influenza effect.
Example 3
Pterostilbene was used for respiratory epithelial cells and to detect expression of NP:
1) a549 cells at 2X 104Inoculating to laser confocal culture dish in 5% CO2Culturing in a cell culture box at 37 ℃ for 24 hours;
2) discard culture supernatant, wash 2 times with PBS, add 200 μ L virus solution (MOI = 1) in 5% CO2Adsorbing the cells for 1h in a cell culture box at 37 ℃;
3) abandoning virus liquid, adding a compound with a specified concentration into a culture dish, arranging a cell control hole and a virus control hole, and continuing to culture for 24 hours;
4) discarding the supernatant, washing with precooled PBS 3 times;
5) fixation and blocking of cells: adding 200 μ L of 4% paraformaldehyde into each well, fixing for 20min, washing with PBS for 3 times, and sealing with 200 μ L of 3% bovine serum albumin solution at room temperature for 1 h;
6) incubating primary antibody: discarding the closed bovine serum albumin solution, adding 200 μ L primary antibody of NP protein diluted with 3% bovine serum albumin solution into each well, and incubating overnight at 4 ℃;
7) hatching a secondary antibody: discarding the primary antibody, washing with 0.05% PBST buffer solution for 3 times, each time for 10 min; adding 200 μ L of second antibody diluted with 3% bovine serum albumin solution, incubating at room temperature for 1h, washing with 0.05% PBST buffer solution for 6 times, each time for 5 min;
8) and (3) cell nucleus staining: adding DAPI cell nuclear dye, dyeing at room temperature for 5min, washing with PBS for 3 times, and adding 200 μ L PBS into each well;
9) and (4) observation: and (3) observing the NP protein in a green part and the cell nucleus in a blue part by selecting different excitation wavelengths through a Laser Scanning Confocal Microscope (LSCM), and randomly selecting 3 visual fields for each hole to shoot the distribution condition of the NP protein in the cell nucleus and the cell cytoplasm.
As shown in fig. 6, the experimental results show that pterostilbene can effectively inhibit the expression of the viral NP protein in the host cells.
Example 4
Pterostilbene was used for respiratory epithelial cells and time point dosing experiments:
1) a549 cells at 2X 104Inoculating to laser confocal culture dish in 5% CO2Culturing in a cell culture box at 37 ℃ for 24 hours;
2) discard culture supernatant, wash 2 times with PBS, add 200 μ L of virus solution (MOI = 1) in 5% CO2Adsorbing cells for 1h in a cell culture box at 37 ℃;
3) abandoning virus liquid, washing with PBS for 2 times, and adding compounds with specified concentration at different time intervals (0-2, 2-5, 5-8, 8-10 and 0-10 h) during single-round virus replication;
4) and 8h after virus infection, discarding the supernatant, washing the supernatant for 2 times by using precooled PBS, and detecting the expression level of the virus NP protein by using Western blot.
As shown in fig. 7, pterostilbene is added at each stage of virus infection for intervention, and has no obvious inhibition effect on NP protein expression at the virus entry stage of 0-2 hours; in the stage of 2-5 hours of gene expression and 5-8 hours of protein synthesis of the virus, pterostilbene has an obvious inhibiting effect on NP protein expression; therefore, pterostilbene mainly acts on the replication stage of viruses after entering host cells.
Example 5
Binding between pterostilbene and NS1 protein:
H1N 1A/puerto Rico/8/1934(H1N1) NS1 Protein was downloaded from Protein Data Bank (PDB number: 3L4Q, resolution: 2.3A). The USCF Chimera is adopted to prepare the structures of protein and ligand molecules, remove solvent molecules and repair protein peptide chains. The molecular surface of the protein was generated with a probe with a radius of 1.4 a using DMS tool in Chimera, spherical aggregates (Spheres) surrounding the active site were generated using the sphgen module, and a Grid file was generated using the Grid module, which was used for fast Grid-based energy scoring evaluation. Flexible docking (flexible docking) was performed using the DOCK6 program, generating 1000 different conformational orientations (orientation) and obtaining electrostatic and van der waals interactions between the compound and residues in the binding pocket, from which Grid scores were calculated. The best scored conformation was obtained by cluster analysis. And finally, analyzing the calculation result through Chimera, and generating a picture by adopting PyMOL.
As shown in fig. 8, NS1 protein plays an important role in viral replication and in regulating the host cell antiviral immune response. The NS1 protein interacts with host cell PI3K protein through its ED domain, interferes with phosphorylation activation of IRF3 after virus infection, and further helps the virus fight against host antiviral immune response. Molecular docking results show that pterostilbene can effectively bind to the ED structure of influenza virus non-structural protein 1 (NS 1) by targeting the HIS169 and GLN563 at amino acid residue positions, and interfere with the regulation effect of influenza NS1 protein.
Example 6
The pterostilbene is used for respiratory epithelial cells and has the regulation and control effects on the PI3K/Akt signal channel after virus infection:
1) a549 cells at 3X 105Perwell in 6-well plates at 37 ℃ with 5% CO2The culture was carried out overnight in an incubator.
2) The supernatant was discarded, cells were washed 2 times with PBS, virus was diluted in serum-free RPMI1640 medium, A549 cells were inoculated at a virus titer of MOI =1, and cells were seeded at 37 ℃ with 5% CO2Adsorbing for 1h in an incubator;
3) after virus infection, virus supernatant was discarded, pterostilbene diluted by multiples of RPMI1640 without serum was added to the cells at 37 ℃ with 5% CO2And continuing culturing in the incubator.
4) After 24 hours, cellular proteins were collected and western blot was used to detect expression of proteins associated with the PI3K/Akt signaling pathway.
As shown in FIG. 9, PI3K protein activates downstream signal molecule Akt to be phosphorylated through interaction between p 85-beta subunit and influenza virus NS1 protein, and helps virus survive in cells by inhibiting apoptosis of virus-infected cells and the like. The experimental results show that the pterostilbene can effectively inhibit the expression of phosphorylated p-Akt after virus infection and obviously reduce the expression, and the effect of the pterostilbene is concentration-dependent.
In conclusion, we speculate that small molecule compound pterostilbene inhibits interaction between NS1 and PI3K by targeting the ED domain of the NS1 protein of influenza virus, and further inhibits activation of a PI3K/Akt signal channel, thereby inhibiting virus infection of host cells.
Claims (3)
1. The application of pterostilbene in preparing anti-influenza A virus drugs is characterized in that the pterostilbene is used as the only active ingredient.
2. The use of pterostilbene of claim 1 in the preparation of a medicament for treating influenza a virus, wherein the pterostilbene targets influenza virus nonstructural protein NS1 and inhibits activation of host PI3K/Akt signaling pathway.
3. The use of pterostilbene of claim 1 in the preparation of a medicament for treating influenza a virus, wherein pterostilbene is formulated into one of an injection, a tablet, a powder, a granule, a capsule, or an oral liquid.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003268599A1 (en) * | 1998-05-05 | 2004-01-22 | Casper, Robert Frederic | Arylhydrocarbon Receptor Ligand Antagonists |
| KR20100038633A (en) * | 2008-10-06 | 2010-04-15 | 한국생명공학연구원 | Pharmaceutical compositions for prevention and treatment of influenza viral diseases containing sophora flavescens extracts, fractions, the isolated pterocarpan and flavonoid compounds therefrom, or the pharmaceutically acceptable salts as an active ingredient |
| KR20100126254A (en) * | 2010-11-19 | 2010-12-01 | 한국생명공학연구원 | Pharmaceutical compositions for prevention and treatment of influenza viral diseases containing sophora flavescens extracts, fractions, the isolated pterocarpan and flavonoid compounds therefrom, or the pharmaceutically acceptable salts as an active ingredient |
| CA3034455A1 (en) * | 2016-09-30 | 2018-04-05 | Nanormics Incorporation Co., Ltd. | Stilbene derivative and preparation method thereof |
| CN111202740A (en) * | 2019-11-19 | 2020-05-29 | 宁夏医科大学 | Application of trifoliate red sandalwood glycoside and antidepressant drug |
| WO2021032591A1 (en) * | 2019-08-16 | 2021-02-25 | Inflazome Limited | Macrocyclic sulfonylurea derivatives useful as nlrp3 inhibitors |
-
2021
- 2021-03-17 CN CN202110287303.6A patent/CN113116872B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003268599A1 (en) * | 1998-05-05 | 2004-01-22 | Casper, Robert Frederic | Arylhydrocarbon Receptor Ligand Antagonists |
| KR20100038633A (en) * | 2008-10-06 | 2010-04-15 | 한국생명공학연구원 | Pharmaceutical compositions for prevention and treatment of influenza viral diseases containing sophora flavescens extracts, fractions, the isolated pterocarpan and flavonoid compounds therefrom, or the pharmaceutically acceptable salts as an active ingredient |
| KR20100126254A (en) * | 2010-11-19 | 2010-12-01 | 한국생명공학연구원 | Pharmaceutical compositions for prevention and treatment of influenza viral diseases containing sophora flavescens extracts, fractions, the isolated pterocarpan and flavonoid compounds therefrom, or the pharmaceutically acceptable salts as an active ingredient |
| CA3034455A1 (en) * | 2016-09-30 | 2018-04-05 | Nanormics Incorporation Co., Ltd. | Stilbene derivative and preparation method thereof |
| CN109790107A (en) * | 2016-09-30 | 2019-05-21 | 奥齐尔公司 | Diphenyl ethylene derivatives and preparation method thereof |
| WO2021032591A1 (en) * | 2019-08-16 | 2021-02-25 | Inflazome Limited | Macrocyclic sulfonylurea derivatives useful as nlrp3 inhibitors |
| CN111202740A (en) * | 2019-11-19 | 2020-05-29 | 宁夏医科大学 | Application of trifoliate red sandalwood glycoside and antidepressant drug |
Non-Patent Citations (4)
| Title |
|---|
| Natural and nature-inspired stilbenoids asantiviral agents;LuceM.Mattio等;《European Journal of Medicinal Chemistry》;20200404;1-20 * |
| 基于 PI3K/Akt 信号通路观察白藜芦醇对呼吸道合胞病毒致肺炎小鼠的保护作用机制;李明等;《中药材》;20200430;第43卷(第4期);986-996 * |
| 紫檀芪介导PI3K/Akt信号通路对人骨肉瘤细胞凋亡与迁移能力的影响;王小伟等;《肿瘤药学》;20180428(第02期);148-152 * |
| 紫檀芪通过PI3K-AKT信号途径抑制缺氧/复氧诱导的乳鼠心肌细胞凋亡;刘峰等;《中国医药科学》;20161115(第21期);38-41 * |
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