Application of glycyrrhizic acid in assisting zinc ions in preparation of anti-respiratory syncytial virus drugs

Abstract

The application discloses application of glycyrrhizic acid assisted zinc ions in preparation of an anti-respiratory syncytial virus drug and relates to the technical field of biological pharmacy. The application of glycyrrhizic acid assisted zinc ions in preparation of the anti-respiratory syncytial virus drug, an effective component of the drug, comprises glycyrrhizic acid and zinc ions, the glycyrrhizic acid assists the zinc ions to enter a cell, and the activity of RdRp enzyme of RSV in a host cell is inhibited; the drug comprises a powder, an oral liquid or a tablet. The application of the glycyrrhizic acid assisted zinc ions in preparation of the anti-respiratory syncytial virus drug can significantly inhibit a replication stage of RSV virus infection and reduce lung damage, and can be widely used for preparation of the anti-respiratory syncytial virus drug.

Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical technology, and in particular to the application of glycyrrhizic acid in assisting zinc ions in the preparation of anti-respiratory syncytial virus drugs. Background Technology

[0002] Respiratory syncytial virus (RSV) is a single-stranded negative-sense RNA virus and a major pathogen causing acute respiratory infections in infants, young children, immunocompromised individuals, and the elderly worldwide. It is characterized by frequent recurrence, rapid transmission, and rapid disease progression. Due to the insufficient immune function and incomplete respiratory development of infants and young children, existing drugs such as ribavirin and pallizumab cannot guarantee effective treatment for them.

[0003] Zinc is an essential trace element for the human body, and zinc supplementation can enhance immunity. Zinc can inhibit the replication process of RNA viruses, thus exhibiting antiviral effects. Clinical trials have demonstrated that oral zinc can reduce the mortality rate of patients infected with the novel coronavirus and shorten the duration of viral infection symptoms. Previous studies have shown that zinc can bind to viral RNA-dependent RNA polymerase (RdRp), thereby inhibiting RdRp enzymatic activity, including in the novel coronavirus and influenza A virus. Viral RdRp is highly conserved among different RNA viruses and is an important target for the development of antiviral inhibitors; therefore, zinc has great potential in combating respiratory syncytial virus (RSV).

[0004] However, common zinc supplements have shown limited efficacy in antiviral treatment. A clinical trial using zinc gluconate to treat patients infected with the novel coronavirus showed that high doses of zinc gluconate, and combinations of ascorbic acid, zinc gluconate, and ascorbic acid, did not significantly shorten the duration of virus-related symptoms. Even if effective, zinc gluconate requires frequent, high-dose administration, which may lead to adverse reactions. This is because zinc is poorly absorbed in the body; it needs to bind with suitable ligands to form a complex before it can be absorbed. Ionophores are metal ion ligands that promote the uptake of metal ions by cells. Studies have shown that quercetin combined with zinc can form a water-insoluble membrane-permeable complex that penetrates the cell membrane, thus acting as a zinc ion carrier and transporting it into the cell. Once inside the cell, the complex dissociates into a single compound due to the low concentration of free and unstable zinc within the cell, thereby providing free zinc ions.

[0005] Glycyrrhizic acid (GA), an active ingredient in traditional Chinese medicine, is a triterpenoid saponin extracted from the roots of licorice. It possesses pharmacological effects such as antiviral and anti-inflammatory properties. Studies have shown that glycyrrhizic acid can enhance cell membrane permeability. In the presence of glycyrrhizic acid, the energy barrier for the calcium channel blocker nifedipine to penetrate the lipid bilayer of the cell membrane decreased from 10 kJ / mol to 5 kJ / mol, thus improving the bioavailability of nifedipine. Glycyrrhizic acid has been shown to adsorb small amounts of water molecules within the membrane, causing localized membrane thinning, and involving a reduction in cholesterol within the lipid bilayer. Glycyrrhizic acid can form stable complexes with cholesterol through the hydrophobic portion of its saponin moiety, helping to clamp cholesterol units. Based on the cell membrane properties of glycyrrhizic acid, it holds promise as an ion carrier, enhancing the absorption and transport of zinc ions in vivo and assisting zinc ions in reaching the antiviral target RdRp located in host cells.

[0006] There are currently no reports of zinc supplementation for the treatment of respiratory syncytial virus (RSV), and the mechanism of action of zinc against RSV is unclear. Furthermore, there are no reports of glycyrrhizic acid acting as an ion carrier to assist zinc ions in transmembrane antiviral activity. Summary of the Invention

[0007] The purpose of this invention is to provide the application of glycyrrhizic acid in assisting zinc ions in the preparation of anti-respiratory syncytial virus (RSV) drugs, which can significantly inhibit the replication phase of RSV infection, reduce lung damage, and can be widely used in the preparation of anti-RSV drugs.

[0008] To achieve the above objectives, the present invention provides the application of glycyrrhizic acid in assisting zinc ions in the preparation of anti-respiratory syncytial virus drugs.

[0009] Furthermore, the active ingredients of the drug include glycyrrhizic acid and zinc ions.

[0010] Furthermore, the concentration ratio of glycyrrhizic acid to zinc ions is 1:1 molar ratio.

[0011] Furthermore, glycyrrhizic acid assists in the entry of zinc ions into cells and inhibits the activity of RdRp enzymes of RSV in host cells.

[0012] Furthermore, the drug includes powder, oral liquid, tablet or gel.

[0013] Furthermore, the gel is a zinc glycyrrhizate gel.

[0014] The advantages and positive effects of the application of glycyrrhizic acid in assisting zinc ions in the preparation of anti-respiratory syncytial virus drugs described in this invention are as follows:

[0015] 1. In this invention, zinc sulfate and glycyrrhizic acid have no significant toxicity to cells within a certain concentration range (the optimal concentration ratio is a molar ratio of 1:1). When glycyrrhizic acid is used in combination with zinc sulfate, the inhibition rate of RSV can reach 70%, which is a relatively high inhibition rate.

[0016] 2. In this invention, with the assistance of glycyrrhizic acid, zinc ions enter the cell, which can significantly inhibit the replication stage of RSV virus infection and effectively inhibit the activity of RSV RdRp enzyme in host cells. It can be widely used to prepare anti-respiratory syncytial virus drugs.

[0017] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0018] Figure 1 The results of cytotoxicity determination of different groups of drugs by CCK-8 assay in this invention are shown, where A is the cytotoxicity result of ZnSO4 and B is the cytotoxicity result of glycyrrhizic acid (GA).

[0019] Figure 2 This invention describes the effects of real-time quantitative PCR on viral load of different samples. A represents the effect of glycyrrhizic acid (GA) on viral load, B represents the effect of ZnSO4 on viral load, C represents the effect of ZnSO4 + 50 μM glycyrrhizic acid (GA) on viral load and EC50, and D represents the effect of ZnSO4 + 100 μM glycyrrhizic acid (GA) on viral load and EC50. EC50 is the half-maximal effective concentration.

[0020] Figure 3 This is the in vitro phased anti-RSV experimental protocol for drugs in this invention;

[0021] Figure 4 These are the results of the in vitro phased anti-RSV experiment of the drug in this invention;

[0022] Figure 5 This is a flowchart of the animal experiment process in this invention;

[0023] Figure 6 This refers to the change in mouse body weight in this invention;

[0024] Figure 7 These are the results of micro CT scans of mouse lungs in this invention;

[0025] Figure 8 This is the result of viral load in mouse bronchoalveolar lavage fluid in this invention;

[0026] Figure 9 HE slices of mouse lungs used in this invention;

[0027] Figure 10 This invention uses ICP-MS to measure changes in intracellular zinc concentration.

[0028] Figure 11 The fluorescence spectrophotometer used in this invention measures changes in the concentration of free zinc ions in cells. Detailed Implementation

[0029] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0030] Unless otherwise defined, the technical or scientific terms used in this invention shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention pertains.

[0031] Example 1: Determination of the cytotoxic effects of different drug groups on A549 cells using the CCK-8 assay.

[0032] 1. Experimental instruments and reagents

[0033] Digital display constant temperature water bath, electronic analytical balance, and biosafety cabinet AC2-3SI are all commercially available.

[0034] 2. Experimental Procedure

[0035] CCK-8 assay principle: The CCK-8 kit is an upgraded alternative to the MTT assay. It is a rapid, highly sensitive, and non-radioactive assay kit based on WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonylbenzene)-2H-tetrazole monosodium salt], widely used for cell proliferation and cytotoxicity. Detection principle: In the presence of an electron coupling reagent, WST-8 can be reduced by mitochondrial dehydrogenases to produce a water-soluble orange-yellow formazan product. The amount of formazan produced is directly proportional to the number of viable cells. Therefore, the more and faster the cell proliferation, the darker the color; the greater the cytotoxicity, the lighter the color. The OD value is measured at a wavelength of 450 nm using a microplate reader, indirectly reflecting the number of viable cells.

[0036] Dosing and detection: Add 100 μL of the solution to each well of a 96-well plate at a density of 2 × 10⁻⁶. 4A549 cell suspension was prepared at 1600 μM / mL. The culture plates were pre-cultured in an incubator at 37°C and 5% CO2 for 24 hours. Glycyrrhizic acid and zinc sulfate (13.2 mg / 10 mL glycyrrhizic acid; 2.6 mg / 10 mL zinc sulfate) were dissolved separately in incomplete culture medium and filtered through a 0.22 μm sterile filter to remove impurities and bacteria. The samples were then diluted with incomplete DMEM high-glucose medium to concentrations of 25, 50, 100, 200, 400, 600, and 800 μM. After removing the culture plates from the culture flasks, the cell supernatant in each well was discarded, and the plates were washed with PBS. 200 μL of the diluted sample was then seeded into each well of a 96-well plate, with six replicates per concentration. Cell control wells were also included. After all wells were prepared, the 96-well plates were labeled and incubated at 37°C and 5% CO2 for 24 hours. The culture was then terminated.

[0037] After terminating the culture, remove the 96-well plate from the incubator and aspirate the supernatant from each well. Wash twice with PBS solution. To avoid errors caused by CCK-8 residue on the pipette tip or well walls during sample addition, mix the CCK-8 with culture medium in the correct proportion before adding 100 μL of sample to each well. Be careful to avoid generating air bubbles in the wells, as this will affect the OD value reading. Incubate the plate in the incubator for 1-4 hours. Measure the absorbance at 450 nm using a microplate reader.

[0038] The formula is as follows:

[0039] Cell viability = [(As-Ab) / (Ac-Ab)] × 100%

[0040] As: Absorbance of experimental wells (including cells, culture medium, CCK-8 solution and drug solution);

[0041] Ac: Absorbance of control wells (containing cells, culture medium, and CCK-8 solution, but excluding drugs);

[0042] Ab: Absorbance of blank wells (containing culture medium and CCK-8 solution, but excluding cells and drugs).

[0043] 3. Experimental Results and Analysis

[0044] like Figure 1 As shown, the cytotoxicity of zinc sulfate and glycyrrhizic acid to A549 cells was detected by the CCK-8 assay kit. The CC50 of zinc sulfate was 588.3 μM (the CC50 of zinc sulfate to A549 cells in the literature was 600 μM), and glycyrrhizic acid had no significant cytotoxicity to cells in the concentration range of 1600 μM.

[0045] Example 2: In vitro inhibition of RSV

[0046] One day before the experiment, 1 mL of a solution with a density of 10⁻⁶ was added to each well of a 24-well plate. 5 A549 cell suspension of cells / mL was prepared, and the culture plate was placed in a clean bench for 15 min to settle before being placed in an incubator for 24 hours (37℃, 5% CO2).

[0047] After the cells grew into a monolayer, glycyrrhizic acid (GA), zinc sulfate, and a mixture thereof were initially diluted to the target concentration using cell culture medium at a non-toxic concentration of 200 μM. Each compound was pre-cultured in A549 cells at 37°C for 1 hour, followed by RSV infection at a fold increase in infection (MOI) of 0.01 for 1 hour. After washing three times with PBS, the sample-containing culture medium was added to each well and the cells were incubated for 24 hours (37°C, 5% CO2). A549 cells were collected, and viral load was detected by qRT-PCR. GAPDH was used as an internal control for quantitative detection.

[0048] Primer sequences are shown in Table 1:

[0049] Table 1

[0050]

[0051] The reaction system (20 μL) is shown in Table 2:

[0052] Table 2

[0053] Primer1 (10μM) 0.4μL Primer2 (10μM) 0.4μL Template DNA / cDNA 1μL <![CDATA[ddH2O]]> 8.2μL

[0054] The reaction procedure is shown in Table 3:

[0055] Table 3

[0056]

[0057] The results are as follows Figure 2 As shown, glycyrrhizic acid had no inhibitory effect on RSV within a concentration range of 100 μM. Figure 2 (A) Zinc sulfate has an inhibitory effect on RSV, but it is not significant. The inhibition rate of 10-200 μM zinc sulfate on RSV is about 30%, and the inhibitory effect is not concentration-dependent. Figure 2 (B); When 50 μM glycyrrhizic acid is used in combination with zinc sulfate, the inhibition rate of RSV by zinc sulfate at concentrations of 50-200 μM is greater than 60%. Figure 2 (C); When 100 μM glycyrrhizic acid was used in combination with zinc sulfate, the inhibition rate of RSV by 25 μM zinc sulfate reached 50%. Figure 2 (D).

[0058] Zinc sulfate showed no EC50 inhibitory effect on RSV in the concentration range of 10-200 μM. After adding 50 μM glycyrrhizic acid, the EC50 was 42.58 μM and the therapeutic index was 13.82. After adding 100 μM glycyrrhizic acid, the EC50 decreased to 22.81 μM and the therapeutic index increased to 25.79.

[0059] Example 3: In vitro antiviral phase assay of combined administration of glycyrrhizic acid and zinc sulfate

[0060] Detailed stages of testing antiviral agents, such as... Figure 3 As shown:

[0061] 1. Adsorption Assay: A549 cells were pre-chilled on ice and then incubated at 4°C for 1 hour with a mixture of 100 μM GA and zinc sulfate and RSV. The cell supernatant was aspirated, and the cells were washed three times with pre-chilled PBS. After adding fresh cell maintenance medium, the cells were incubated in a 37°C, 5% CO2 cell culture incubator for 24 hours. A model group without drug administration was also set up, with 4 replicates per group. A549 cells were collected, and viral load was detected by qRT-PCR.

[0062] 2. Internalization Assay: A549 cells were pre-chilled on ice, infected with viral solution at 4°C for 1 h to allow viral attachment without internalization. Cells were washed three times with pre-chilled PBS solution, then incubated with a mixture of 100 μM GA and zinc sulfate at 37°C for 1 h. After removing the supernatant, fresh culture medium was added, and the cells were incubated in a 37°C, 5% CO2 cell culture incubator for 24 h. A control group without drug administration was also included, with four replicates per group. A549 cells were collected, and viral load was detected by qRT-PCR.

[0063] 3. Replication (viral mRNA synthesis) assay: A549 cells were infected with viral solution at 37°C for 2 hours to allow sufficient viral entry into the cells. The cells were washed three times with PBS solution, then incubated with a mixture of 100 μM GA and zinc sulfate at 37°C for 6 hours. After removing the supernatant, fresh culture medium was added, and the cells were incubated in a 37°C, 5% CO2 cell culture incubator for 24 hours. A model group without drug administration was also set up, with four replicate wells per group. A549 cells were collected, and viral load was detected by qRT-PCR.

[0064] 4. Release Assay: A549 cells were infected with viral solution at 37°C for 2 hours to allow sufficient viral entry into the cells. The cells were washed three times with PBS, then incubated with fresh culture medium at 37°C and 5% CO2 for 8 hours. During this time, the virus formed new viral particles and was released from the host cells. After removing the supernatant, a mixed solution containing 100 μM GA and zinc sulfate was added, and the cells were incubated at 37°C and 5% CO2 for 24 hours. A model group without drug administration was also set up, with four replicates per group. A549 cells were collected, and viral load was detected by qRT-PCR.

[0065] The results are as follows Figure 4 As shown, zinc sulfate has a certain inhibitory effect on the entry and replication phases of RSV, but the inhibition rate is less than 50% and is not significant. The combined use of 100 μM glycyrrhizic acid and 100 μM zinc sulfate significantly inhibited RSV replication at a rate of 61.6%. This indicates that, with the assistance of glycyrrhizic acid, zinc can significantly inhibit the replication phase of RSV infection. The mechanism may be that glycyrrhizic acid assists zinc ions in entering cells, effectively inhibiting the activity of RSV's RdRp enzyme in host cells.

[0066] Example 4: In vivo inhibition of RSV by drugs

[0067] Animal experimentation procedures are as follows Figure 5 As shown, the acclimatization process was conducted after 7 days, with a 3-day period from model establishment to euthanasia. In vivo drug dosages are shown in Table 4.

[0068] Table 4

[0069]

[0070] 1. RSV infection of Balb / c mouse model to establish mouse model

[0071] First, mice in each group were anesthetized using an air anesthesia machine. Once fully anesthetized, the mice were quickly removed. Except for the control group, 80 μL of RSV-A2 (7.0 × 10⁻⁶) was added to the nostrils of each mouse using a pipette. 7 PFU). After nasal instillation, on day 1, mice were administered 0.2 mL / mouse of the prepared drugs in this chapter via gavage. The blank control group and the virus model group received the same volume of physiological saline. Mouse weight was monitored starting 3 days before nasal instillation. Changes in mouse weight were observed, and the results are as follows: Figure 6 As shown, the body weight of mice in the model group continued to decrease 3 days after modeling. Except for the blank group, the body weight of mice in all groups decreased significantly, which may be due to viral infection.

[0072] 2. MicroCT scan of the lungs to observe lung infection in mice of each group.

[0073] On the second day, CT scans were performed on six groups of mice. High-resolution X-ray imaging technology is typically used. During the scan, the animals are anesthetized with isoflurane gas beforehand, quickly placed in the appropriate position, and a mask containing isoflurane gas is placed on the mouse's face. Fine-tuning is performed using a micro-adjuster to ensure that the lungs are at the optimal scanning angle for multi-angle imaging.

[0074] The results are as follows Figure 7 As shown, compared to the blank group and the positive control group, significant bronchiectasis was observed in the lung CT scans of the model group, zinc sulfate group, and glycyrrhizic acid group, with diffuse distribution of flocculent and ground-glass opacities in both lungs. Treatment with zinc glycyrrhizic acid reduced lung infection in the mice.

[0075] 3. Determination of viral load in bronchoalveolar lavage fluid of mice

[0076] On the third day of the experiment, after shaving one side of the beard, blood was collected from the eyeball in an EP tube and incubated at 4°C for 15 minutes. Then, the tube was centrifuged at 3500 rpm for 10 minutes at 4°C. The supernatant was collected and stored in a new EP tube at -80°C. After blood collection, the mice were euthanized by dislocation. Lung tissue, lung pathology (right middle lobe), spleen tissue, and thymus tissue were collected, blotted dry on filter paper, and weighed. A bronchoalveolar lavage fluid apparatus (using a gavage needle connected to an indwelling intravenous catheter) and pre-cooled PBS (containing 1% FBS) were prepared. A 1 mL syringe containing the bronchoalveolar lavage fluid apparatus was used to draw in the cold PBS, removing all air bubbles, and placed on ice. The mice were then grasped, blood was released from the eyeballs, and the limbs were dislocated to euthanize the mice without damaging the trachea. After the mice were completely dead, their fur was moistened with alcohol. The mice were laid flat on a foam board, their limbs were fixed, the skin on the neck was cut open, tissues and muscles were dissected, and the trachea was separated. A small incision was made in the trachea (near the head) using ophthalmic scissors. Carefully insert the intravenous catheter into the trachea through a small opening. Connect a 1 mL syringe to the catheter and slowly inject 500 μL of pre-cooled PBS. Gently massage the mouse's chest for 15–20 seconds while rhythmically pressing the chest and simultaneously withdrawing the syringe (volume to 700–800 μL). The first irrigation typically yields 300 μL of irrigation fluid. Repeat the irrigation several times to obtain approximately 500 μL of irrigation fluid. Collect the fluid in an EP tube and store at -80°C. Measure the RSV viral titer using RT-qPCR.

[0077] The results are as follows Figure 8 As shown, compared with the model group, glycyrrhizic acid inhibited RSV by 24%, and zinc sulfate inhibited RSV by 40%, with no significant inhibitory effect. Ribavirin inhibited RSV by 67%, and the zinc glycyrrhizate complex inhibited RSV by 73%, showing significant inhibitory effects. The zinc glycyrrhizate group showed significant anti-RSV activity, while the zinc sulfate and glycyrrhizic acid groups showed some anti-RSV activity, but it was not significant.

[0078] 4. HE section analysis to determine lung infection in mice of each group.

[0079] On day 3 of the experiment, after euthanizing the mice, fresh lung tissue measuring 0.3*0.3*0.3cm was taken from each group of mice, fixed with 4% paraformaldehyde for 24 hours, embedded in paraffin, and cut into complete tissue sections with a thickness of 4μm using a microtome. After dewaxing, the tissue was stained with hematoxylin and eosin (HE), and the inflammation of each group of lung tissue was observed under an optical microscope.

[0080] The results are as follows Figure 9 As shown, the alveolar walls of mice in the glycyrrhizic acid group were ruptured and congested, and there was significant inflammatory cell infiltration between the alveoli; after treatment with the glycyrrhizic acid zinc complex group and the zinc sulfate group, the inflammatory cell infiltration was significantly improved, and the alveolar wall structure was basically intact.

[0081] Example 5: Cellular uptake experiment of the drug

[0082] 1. ICP-MS was used to measure changes in intracellular zinc concentration to investigate the effect of GA on intracellular zinc concentration.

[0083] 1×10 5 Live cells were seeded in 6-well plates (3 mL of culture medium per well) and incubated for 24 h. Cells were individually exposed to three solutions: Group 1: 100 μM zinc sulfate; Group 2: 50 μM glycyrrhizic acid and 100 μM zinc sulfate; and Group 3: 100 μM glycyrrhizic acid and 100 μM zinc sulfate. Zinc sulfate and glycyrrhizic acid were diluted with DMEM medium, and the drugs were added to each group. The cells were incubated at 37°C for 6 h. Afterward, the culture medium was aspirated, and the cells were washed three times with PBS. 200 μL of NP-40 cell lysis buffer was added, and adherent cells were scraped off with a cell scraper. The cell lysate was collected and centrifuged at 12000 g for 10 minutes at 4°C. Protein concentration was determined using a BCA protein assay kit. 0.1 mL of the lysate was placed in a digestion vessel, and 0.8 mL of concentrated nitric acid and 0.1 mL of H₂O₂ solution were added. The sample was then placed in a microwave digester for digestion. After the sample digestion is complete, dilute to a volumetric flask with 10 mL of water, shake well to obtain the test solution, and determine the Zn content by ICP-MS.

[0084] The results are as follows Figure 10 As shown, the combined use of 50 μM and 100 μM glycyrrhizic acid with 100 μM zinc sulfate can significantly increase the concentration of zinc in cells.

[0085] 2. Changes in intracellular free zinc ion concentration were measured using a fluorescence spectrophotometer to investigate the effect of GA on intracellular free zinc ion concentration.

[0086] 1×10 5Live cells were seeded in 6-well plates (3 mL of culture medium per well) and incubated for 24 h. A549 cells were seeded in cell culture dishes, and after cell attachment, the culture medium was aspirated and the cells were washed with PBS. Zinc sulfate and glycyrrhizic acid were then diluted with DMEM, and the drugs were added in groups. The cells were incubated at 37°C for 6 h. Afterward, the culture medium was aspirated, and 20 μM Zinquin ethylester probe (diluted in PBS) was loaded. The cells were incubated at 37°C for 30 min, washed with zinc-free PBS, and resuspended. The fluorescence intensity was measured using a fluorescence spectrophotometer (Ex: 368 nm, Em: 480 nm).

[0087] The results are as follows Figure 11 As shown, based on the fluorescence intensity of each group of zinc ion fluorescent probes, compared with the blank group, the effects of 50 μM and 100 μM zinc sulfate on increasing the concentration of free zinc ions in cells were small and similar. However, the concentration of free zinc ions in cells after adding 100 μM glycyrrhizic acid was significantly higher than that in the blank group and the zinc sulfate-only group. This indicates that the combined use of 50 μM and 100 μM glycyrrhizic acid with 100 μM zinc sulfate can significantly increase the concentration of free zinc ions in cells.

[0088] Therefore, the application of glycyrrhizic acid to assist zinc ions in the preparation of anti-respiratory syncytial virus drugs in this invention can significantly inhibit the replication stage of RSV virus infection and reduce lung damage. It can be widely used in the preparation of anti-respiratory syncytial virus drugs.

[0089] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. The application of glycyrrhizic acid assisting zinc ions in the preparation of an anti-respiratory syncytial virus drug, wherein the active ingredients of the drug are glycyrrhizic acid and zinc ions, and the concentration ratio of glycyrrhizic acid to zinc ions is a molar ratio of 1:1; the concentration of glycyrrhizic acid is 100 μM, and the concentration of zinc ions is 100 μM.

2. The application according to claim 1, characterized in that: Glycyrrhizic acid acts as a carrier of zinc ions, assisting zinc ions in entering cells and inhibiting the activity of RdRp enzyme of RSV in host cells, thereby inhibiting respiratory syncytial virus.

3. The application according to claim 1, characterized in that: The drug is in the form of powder, oral liquid, tablet or gel.

4. The application according to claim 3, characterized in that: The gel is zinc glycyrrhizate gel.

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