Broad-spectrum antiviral Chinese medicine monomer batroxoline, and its pharmaceutical composition and application

Abstract

The present invention discloses a broad-spectrum antiviral Chinese medicine monomer, which is baucaryl or its derivatives. The present invention also discloses a broad-spectrum antiviral pharmaceutical composition, which includes active ingredients baucaryl and / or its derivatives, and one or more pharmaceutically acceptable salts thereof and pharmaceutically acceptable carriers or diluents thereof. The present invention also discloses the use of the broad-spectrum antiviral Chinese medicine monomer baucaryl and its pharmaceutical composition as a viral infection inhibitor and / or in the preparation of drugs for preventing and treating viral infectious diseases. The innovation of the present invention is the discovery of baucaryl that can widely inhibit multiple viruses from infecting host cells, providing a new way and means for the prevention and treatment of multiple viral infectious diseases, which has important research and development value and development significance.

Description

Technical Field

[0001] The present invention relates to the technical field of antiviral drugs, and in particular to a broad-spectrum antiviral Chinese medicine monomer daurosoline, and a pharmaceutical composition and application thereof. Background Art

[0002] Viral infectious diseases are highly contagious and pathogenic, and are a huge threat to human health. Specific vaccines and antiviral drugs are the most effective tools to fight viral infections. However, due to the wide variety of viruses in nature, many viruses have a high ability to mutate, which greatly increases the research and development cycle and cost of specific vaccines and antiviral drugs. Currently, vaccination is the main means of preventing influenza virus infection, but the update speed of the vaccine lags behind the mutation of the influenza virus, which makes conventional seasonal vaccines ineffective in preventing and treating viruses. Clinically existing influenza viruses are also constantly developing drug resistance, which affects the therapeutic effect of existing anti-influenza virus drugs. Therefore, it is of great significance to develop effective new broad-spectrum antiviral drugs.

[0003] Traditional Chinese medicine plays an important role in viral infectious diseases. Its role in viral infection has received great attention from experts and scholars at home and abroad. The treatment of viral infectious diseases with traditional Chinese medicine has once again become a hot topic. People are increasingly keen to find drugs or lead compounds for the treatment of major diseases from natural plants. Therefore, there is an urgent need to develop new antiviral drugs in clinical practice. Viral infections belong to the categories of "plague" and "febrile diseases" in traditional Chinese medicine. They are caused by the feeling of untimely air or epidemic evil, which is contained in the lungs and stomach and causes diseases. Therefore, using modern scientific research methods and technologies to discover new antiviral drugs from traditional Chinese medicine will definitely be a major trend in future antiviral research and is practically feasible.

[0004] Batrysoline, also known as benzimidazole, is an alkaloid extracted from the rhizome of the plant Batrysoline of the Menispermaceae family. It is the main component of Batrysoline phenolic alkaloids and belongs to the dibenzyltetrahydroisoquinoline alkaloids. Studies have shown that Batrysoline has the characteristics of Class III antiarrhythmic drugs. The drug has broad prospects for clinical application, but the application of Batrysoline in antiviral treatment has not been reported. Summary of the invention

[0005] An object of the present invention is to solve at least the above problems and / or disadvantages and to provide at least the advantages which will be described hereinafter.

[0006] Another object of the present invention is to provide a broad-spectrum antiviral Chinese medicine monomer.

[0007] Another object of the present invention is to provide a broad-spectrum antiviral pharmaceutical composition.

[0008] Another object of the present invention is to provide a broad-spectrum antiviral Chinese medicine monomer or composition for use as a viral infection inhibitor and / or in the preparation of drugs for preventing and treating viral infectious diseases.

[0009] To this end, the technical solution provided by the present invention is:

[0010] A broad-spectrum antiviral Chinese medicine monomer, which is Daurisoline (DAS) or its derivatives.

[0011] The structural formula of dauroxetine is as follows:

[0012]

[0013] A broad-spectrum antiviral pharmaceutical composition comprising dauroxaline and / or its derivatives as active ingredients.

[0014] Preferably, the broad-spectrum antiviral pharmaceutical composition further comprises one or more pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier or diluent thereof.

[0015] Preferably, the antiviral pharmaceutical composition is in the form of a solid preparation, an injection, an inhalation preparation, a spray, a liquid preparation, an emulsion or a compound preparation.

[0016] The antiviral Chinese medicine monomer or the antiviral pharmaceutical composition, the derivative of dauphinolamine is a pharmaceutically acceptable salt of dauphinolamine, a solvate of dauphinolamine, or a hydrate of dauphinolamine.

[0017] The antiviral Chinese medicine monomer or the antiviral pharmaceutical composition is used as a viral infection inhibitor and / or in the preparation of drugs for preventing and / or treating viral infectious diseases.

[0018] Preferably, in the application, the virus is one or more of vesicular stomatitis virus (VSV), adenovirus (ADV), encephalomyocarditis virus (EMCV), influenza A virus (H1N1).

[0019] Preferably, the use, inhibitor or drug is a mammalian drug.

[0020] Preferably, in the application, the mammal is bovine, equine, ovine, porcine, canine, feline, rodent or primate.

[0021] The present invention has at least the following beneficial effects:

[0022] The present invention verifies that daurosuline has a strong anti-multiple viral effect at the cellular level by detecting the cytotoxicity of daurosuline in human non-small cell lung cancer cells A549 (derived from the ATCC cell bank) and its antiviral activity against multiple viruses, and can be used to prepare a new broad-spectrum antiviral infectious disease drug. The present invention proves that daurosuline has the function of inhibiting viral proliferation at both the cellular and animal levels.

[0023] The present invention is an expansion of the clinical application of dauroxamine.

[0024] definition

[0025] To facilitate understanding of the present invention, the meanings of the terms and phrases used in the present invention are defined as follows:

[0026] Biopharmaceuticals: Biopharmaceuticals refer to products used for prevention, treatment and diagnosis that are manufactured from organisms, biological tissues, cells, organs, body fluids, etc., using the research results of microbiology, biology, medicine, biochemistry, etc., and comprehensively utilizing the scientific principles and methods of microbiology, chemistry, biochemistry, biotechnology, pharmacy, etc. The raw materials of biopharmaceuticals are mainly natural biological materials, including microorganisms, human bodies, animals, plants, marine organisms, etc.

[0027] Pharmacology: Pharmacology is a science that studies the interaction between drugs and the body and the mechanism of drug action. It mainly includes two aspects: pharmacodynamics and pharmacokinetics. The former explains the effects and action principles of drugs on the body, while the latter explains the processes of drug absorption, distribution, biotransformation and excretion in the body, as well as the laws of drug effects and blood drug concentrations over time.

[0028] Other advantages, objectives and features of the present invention will be embodied in part through the following description, and in part will be understood by those skilled in the art through study and practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is a proliferation-toxicity detection diagram of DAS at the cellular level (in non-small cell lung cancer cells A549) in Example 1 of the present invention, wherein a is the toxicity of DAS to A549 cells after 24 hours of incubation, and b is the toxicity of DAS to A549 cells after 12 hours of incubation;

[0030] Figure 2: This is a graph showing the detection result of DAS inhibiting the replication of VSV-eGFP virus at the cellular level in Example 2 of the present invention, wherein a is the flow cytometry detection result of DAS inhibiting the virus by co-incubating VSV-eGFP virus and DAS, i.e., adding drugs during the entire virus infection process, b is a bar graph of a, c is the qPCR detection result of DAS inhibiting VSV virus in A549 cells, and d is the Western Blot detection result of DAS inhibiting VSV virus in A549 cells;

[0031] Figure 3 : This is a graph showing the detection result of DAS inhibiting the replication of ADV-eGFP virus at the cellular level in Example 3 of the present invention, wherein a is the flow cytometry detection result of DAS inhibiting the virus when ADV-eGFP virus and DAS are co-incubated, i.e., the drug is added during the whole process of virus infection, and b is a bar chart of a;

[0032] Figure 4 This is a qPCR test result diagram of DAS in Example 4 of the present invention inhibiting EMCV virus replication at the cellular level;

[0033] Figure 5 The figure is a graph showing the detection result of DAS inhibiting H1N1 virus replication in A549 cells in Example 5, wherein a is the qPCR detection result of DAS inhibiting H1N1 virus in A549 cells; b is a graph showing the Western Blot result of DAS inhibiting H1N1 virus NP protein replication at the protein level; c is a graph showing the plaque assay result of DAS against H1N1 virus replication in MDCK cells;

[0034] Figure 6 This is a qPCR test result diagram of DAS in Example 6 of the present invention inhibiting H1N1 virus replication at the cellular level, which includes five administration methods: administration by DAS pretreatment, administration during virus adsorption, administration during virus entry, administration after virus entry, and administration throughout virus infection;

[0035] Figure 7 This is a graph showing the detection results of DAS in Example 7 of the present invention inhibiting H1N1 virus replication at the animal level, wherein a is a curve diagram of mouse weight changes, and b is a CT image of mouse lungs. DETAILED DESCRIPTION

[0036] The present invention is further described in detail below in conjunction with the accompanying drawings so that those skilled in the art can implement the invention with reference to the description.

[0037] It should be understood that terms such as “having”, “including” and “comprising” used herein do not specify the existence or addition of one or more other elements or combinations thereof.

[0038] The pharmacological effects of bat gynecology are very extensive. It not only has pharmacological activities such as antibacterial and anti-inflammatory based on traditional efficacy, but also has biological activities such as protecting the cardiovascular system, anti-tumor, anti-depression, and anti-Alzheimer's disease. In addition to the above-mentioned pharmacological effects of bat gynecology, does it have the effect of inhibiting viral replication? In-depth clarification of the antiviral effect of bat gynecology is the focus of expanding the medicinal value of bat gynecology, and it is also the difficulty in developing broad-spectrum antiviral drugs.

[0039] The present invention provides a broad-spectrum antiviral Chinese medicine monomer, which is Daurisoline (DAS).

[0040] The present invention also provides a broad-spectrum antiviral pharmaceutical composition, which comprises active ingredients dauroxaline and / or its derivatives.

[0041] In the above scheme, preferably, the broad-spectrum antiviral pharmaceutical composition further comprises one or more pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier or diluent thereof.

[0042] In the above scheme, preferably, the antiviral pharmaceutical composition is in the form of a solid preparation (tablet, capsule, pill, granule), injection, inhalation preparation, spray, liquid preparation (oral solution), emulsion or compound preparation.

[0043] The antiviral Chinese medicine monomer or the antiviral pharmaceutical composition, the derivative of daurosuline is a pharmaceutically acceptable salt of daurosuline or a solvate of daurosuline or a hydrate of daurosuline. The derivative of daurosuline also includes but is not limited to stereoisomers, tautomers, homologues, prodrugs or polymorphs of daurosuline.

[0044] The antiviral Chinese medicine monomer or the antiviral pharmaceutical composition is used as a viral infection inhibitor and / or in the preparation of drugs for preventing and / or treating viral infectious diseases.

[0045] In the above scheme, preferably, the virus includes one or more of vesicular stomatitis virus (VSV), adenovirus (ADV), encephalomyocarditis virus (EMCV), and influenza A virus (H1N1).

[0046] In the above embodiment, the inhibitor or drug is preferably a drug for mammals.

[0047] In the above scheme, preferably, the mammal is bovine, equine, ovine, porcine, canine, feline, rodent or primate (primates include primitive monkeys, capuchins, giant lemurs, aye-aye, loris, cynomolgus, mouse lemurs, advanced monkeys, apes, humans, white-cheeked gibbons, tarsiers, capuchins, green monkeys, saki-faced monkeys, spider monkeys, monkeys, gibbons, orangutans, and hominids.).

[0048] In order to enable those skilled in the art to better understand the technical solution of the present invention, the following embodiments are provided for illustration:

[0049] Example 1

[0050] Proliferation-toxicity assay of DAS at the cellular level

[0051] Different concentrations (0.0625, 0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 32, 64, 128, 256 μM) of DAS were added to lung cancer human alveolar basal epithelial cells A549 cultured in 96-well plates, with 3 replicates for each concentration. After incubation for 24 h or 12 h, CCK8 reagent was added, and the cells were incubated at 37° for 30 min. The absorbance at 450 nm was detected by a microplate reader.

[0052] like Figure 1 The results showed that the IC of DAS in A549 cells after 24 h of incubation 50 The IC value of 85.8 μM for 12 h 50 It is 104.4μM.

[0053] Example 2

[0054] DAS inhibits VSV viral replication at the cellular level

[0055] In order to determine the effect of DAS on VSV virus replication, the inventors conducted research using a variety of detection methods, including flow cytometry to detect the percentage of GFP-positive cells, Western Blot to detect the expression of VSV virus G protein, and qPCR to detect the relative abundance of VSV virus RNA. The specific dosing and detection methods are as follows:

[0056] Flow cytometry detection: GFP-tagged vesicular stomatitis virus (VSV-eGFP) (MOI = 0.05) and different concentrations (5, 10, 20 μM) of daurine were added to A549 cells (cell volume 1.5×10 5 / well), after incubation for 12 hours, the cells were collected for flow cytometry detection of the percentage of GFP-positive cells. qPCR detection: A549 cells were treated with different concentrations (5, 10, 20 μM) of batrysoline, and VSV virus (MOI = 0.05, infection for 12 hours) was added at the same time. After incubation for the corresponding time, the cells were collected to extract RNA, and the changes in viral load in the cells were detected by qPCR. Western Blot detection: A549 cells were treated with different concentrations of DAS (5, 10, 20 μM) and infected with VSV virus (MOI = 0.1). After 16 hours, the cells were collected, and the expression of VSV virus G protein was detected by Western Blot after protein extraction. The experiment was repeated 3 times independently. There was a statistical difference between the experimental group and the control group. The results are expressed as mean ± standard error, ***, p < 0.001.

[0057] Figure 2 The results show that DAS inhibits VSV viral replication at the cellular level.

[0058] Flow cytometry results showed that treatment of A549 cells with daurine could reduce the percentage of GFP-positive cells in a dose-dependent manner (5, 10, 20 μM). Figure 2 a), the bar graph shows the percentage of GFP positive cells ( Figure 2 b), ***p<0.001 (extremely significant difference). The higher the GFP positive ratio, the stronger the VSV virus replication. After adding DAS, the GFP positive rate decreased, proving that DAS can inhibit VSV virus replication. The qPCR test results showed that VSV virus amplification was obvious in the control group, while the experimental group with DAS significantly inhibited viral gene expression in a dose-dependent manner, with the most significant inhibition at a drug concentration of 20μM ( Figure 2 c), Western Blot results showed that as the concentration of DAS increased, the expression of VSV virus G protein gradually weakened or even disappeared completely ( Figure 2 d). These results indicate that daurocandin can effectively inhibit VSV viral replication at the cellular level.

[0059] Example 3

[0060] DAS inhibits ADV viral replication at the cellular level

[0061] In order to determine the effect of DAS on ADV virus replication, the inventors detected the percentage of GFP-positive cells by flow cytometry, and used a bar graph to count the percentage of GFP-positive cells. The percentage of GFP-positive cells represents the replication of ADV virus. The higher the GFP-positive ratio, the stronger the ADV replication. The specific dosing method is as follows:

[0062] Adenovirus ADV virus (ADV-eGFP) with GFP tag (MOI = 5) and different concentrations (10, 20, 40 μM) of daurine were added to A549 cells (cell volume 1.5×10 5 / well), and after 12h of co-incubation, cells were collected for flow cytometry to detect the percentage of GFP-positive cells. The experiment was repeated 3 times independently, and there was a statistical difference between the experimental group and the control group. The results are expressed as mean ± standard error, ***, p < 0.001.

[0063] Figure 3 The results show that DAS inhibits ADV-eGFP viral replication at the cellular level.

[0064] like Figure 3 The results showed that the treatment of A549 cells with daurine could reduce the percentage of GFP-positive cells in a dose-dependent manner (10, 20, 40 μM). The bar graph showed the percentage of GFP-positive cells, ***p<0.001 (extremely significant difference). The higher the GFP-positive ratio, the stronger the ADV virus replication. After adding DAS, the GFP-positive rate decreased, proving that DAS can inhibit ADV virus replication during the entire administration.

[0065] Example 4

[0066] DAS inhibits EMCV viral replication at the cellular level

[0067] In order to determine the effect of DAS on EMCV virus replication, the inventors used EMCV (encephalomyocarditis virus) to infect A549 cells and detect the effect of DAS on virus replication. Specifically, A549 cells were treated with batracholine at different concentrations (5, 10, 20 μM), and EMCV virus (MOI = 3, infection 8h) was added at the same time. After incubation for the corresponding time, the cells were collected to extract RNA, and qPCR was used to detect changes in viral load in the cells. The experiment was repeated 3 times independently, and there was a statistical difference between the experimental group and the control group. The results are expressed as mean ± standard error, ***, p < 0.001.

[0068] Figure 4 The qPCR results of DAS inhibition of EMCV virus in A549 cells are shown.

[0069] like Figure 4The results showed that the EMCV virus amplified significantly in the control group, while the experimental group with the addition of DAS significantly inhibited viral gene expression in a dose-dependent manner, with the most significant inhibition at 20 μM. After the virus infects the host, it releases the viral genome and then uses the host cell resources to amplify the progeny virus. The strength of viral gene expression can reflect the amplification of the virus in the host. After DAS treated the cells, viral gene expression was inhibited, indicating that DAS can effectively resist EMCV virus infection.

[0070] Example 5

[0071] DAS inhibits H1N1 virus replication at the cellular level

[0072] In order to determine the effect of DAS on H1N1 virus replication, the inventors used H1N1 (influenza A virus) to infect A549 cells and detected the effect of DAS on virus replication by qPCR, Western Blot and plaque assay. The details are as follows:

[0073] qPCR detection: A549 cells were treated with different concentrations (5, 10, 20 μM) of batrysoline, and H1N1 virus (MOI = 0.05, infection for 12 hours) was added. After incubation for the corresponding time, the cells were collected to extract RNA, and the changes in viral load in the cells were detected by qPCR. Western Blot detection: A549 cells were treated with different concentrations of DAS (5, 10, 20 μM) and infected with H1N1 virus (MOI = 0.1). After 16 hours, the cells were collected, and the expression of H1N1 virus NP protein was detected by Western Blot after protein extraction. Plaque assay detection: A549 cells were treated with 20 μM DAS, and H1N1 (MOI = 0.05) was added. After infection for 12 hours, the cell culture supernatant was collected, and then the supernatant containing the virus was diluted 100 times and added to MDCK cells (cell size 1.7×10 5 / well), and then place the cell culture plate in a cell culture incubator at 37°, 5% CO2 for incubation for 2h. After incubation, rinse with PBS twice. Wash away the unadsorbed virus. Heat and melt the 2% agar, cool it to below 40°, mix it with DMEM culture medium at a volume ratio of 1:1, and add TPCK-trypsin to mix until the concentration is 1μg / mL. Gently add the agar covering liquid to the 24-well cell culture plate, adding 500μL to each well. After standing and solidifying at room temperature, invert it in a cell culture incubator at 37°, 5% CO2 for incubation. After culturing for 2-3 days, take it out, add 500μL of 4% paraformaldehyde to each well of agar, fix it for 30min, then pour out the agarose, add 0.1% crystal violet 200μl / well to stain for 15min, finally wash off the crystal violet in water, and observe the number of plaques. The experiment was repeated three times independently. There were statistical differences between the experimental group and the control group. The results are expressed as mean ± standard error, ***, p < 0.001.

[0074] Figure 5 The results show that DAS inhibits H1N1 virus at the cellular level.

[0075] qPCR results showed that H1N1 virus amplification was obvious in the control group, while the experimental group added with DAS significantly inhibited viral gene expression in a dose-dependent manner ( Figure 5 a); Western Blot results showed that as the concentration of DAS increased, the expression of H1N1 virus NP protein gradually weakened or even disappeared completely ( Figure 5 b); Plaque assay found that DAS can dose-dependently (5, 10, 20 μM) reduce the number of plaques formed by H1N1 virus on 24-well plates ( Figure 5 c) The more plaques there are, the higher the titer of the H1N1 virus is. After adding DAS, the number of plaques decreases, which means that DAS can inhibit the replication ability of the H1N1 virus.

[0076] Example 6

[0077] Effects of DAS on the replication life cycle of H1N1 virus

[0078] In order to determine which stage of the H1N1 life cycle DAS affects to inhibit its replication, the inventors treated cells with different dosing methods, including pre-treatment dosing, dosing during virus adsorption, dosing during virus entry, dosing after virus entry, and dosing throughout the virus infection. After incubation for a corresponding period of time, cells were harvested to extract RNA, and qPCR was used to detect changes in viral load in cells. The specific dosing methods are as follows:

[0079] Drug pretreatment experiment: Different concentrations (10, 20 μM) of DAS were added to A549 cells (cell volume 1.5×105 / well), after incubation for 12 hours, fresh medium was replaced and HIN1 virus (MOI = 0.1) was added for another 12 hours, cells were harvested to extract RNA, and qPCR was used to detect changes in viral load in cells. The experiment was repeated 3 times independently, and there was a statistical difference between the experimental group and the control group. The results are expressed as mean ± standard error, ***, p < 0.001.

[0080] Drug administration during virus adsorption: H1N1 virus (MOI = 0.1) and different concentrations (10, 20 μM) of DAS were added to A549 cells (cell volume 1.5×10 5 / well), adsorbed at 4℃ for 2h, then replaced with fresh medium and continued incubation for 12h, cells were harvested to extract RNA, and qPCR was used to detect changes in viral load in cells. The experiment was repeated 3 times independently, and there was a statistical difference between the experimental group and the control group. The results are expressed as mean ± standard error, ***, p < 0.001.

[0081] Drug administration during virus entry: A549 cells were infected with H1N1 virus (MOI = 0.1), adsorbed at 4 ° C for 2 hours, replaced with complete medium containing different concentrations (10, 20 μM) of DAS, incubated at 37 ° C for 1.5 hours, and then replaced with fresh medium for further incubation for 12 hours. The cells were harvested to extract RNA, and the changes in viral load in the cells were detected by qPCR. The experiment was repeated 3 times independently, and there was a statistical difference between the experimental group and the control group. The results are expressed as mean ± standard error, ***, p < 0.001.

[0082] Drug administration after virus entry: A549 cells were infected with H1N1 virus (MOI = 0.1), adsorbed at 4 ° for 2 hours, then replaced with fresh medium, incubated at 37 ° for 1.5 hours, replaced with complete medium containing different concentrations (10, 20 μM) of DAS, and incubated for another 12 hours. Cells were harvested to extract RNA, and qPCR was used to detect changes in viral load in cells. The experiment was repeated 3 times independently, and there was a statistical difference between the experimental group and the control group. The results are expressed as mean ± standard error, ***, p < 0.001.

[0083] Drug treatment: H1N1 virus (MOI = 0.1) and different concentrations (10, 20 μM) of DAS were added to A549 cells (cell volume 1.5×10 5 / well), after 12 hours of incubation, cells were collected to extract RNA, and qPCR was used to detect changes in viral load in cells. The experiment was repeated 3 times independently, and there was a statistical difference between the experimental group and the control group. The results are expressed as mean ± standard error, ***, p < 0.001.

[0084] Figure 6 Results showing that DAS inhibits H1N1 virus replication at the cellular level.

[0085] like Figure 6 The results showed that DAS showed different results in inhibiting H1N1 virus replication in different dosing methods. Among them, DAS had the most significant effect in inhibiting H1N1 virus replication when administered during the virus entry process and during the entire virus infection process, and significantly inhibited viral gene expression in a dose-dependent manner.

[0086] Example 7

[0087] Effects of DAS on body weight changes and lung infection in H1N1 infected mice

[0088] Animal in vivo experiments reflect the antiviral effect of the body at the overall level and are closer to the reaction mechanism in the human body, so the inventors conducted a study on the anti-H1N1 virus effect of batryticatine in mice.

[0089] Six groups of C57BL / 6 mice (6-8 weeks old healthy female mice, weighing about 20-22 g) were set up, namely CON group (blank control group), H1N1 group (model group), oseltamivir group (positive drug group), DAS (30 mg kg -1 ). Except for the CON group, mice in other groups were infected with H1N1 virus through the nose. The drug-treated group was gavaged with 200 μl / mouse according to the corresponding dose. The CON group and the H1N1 group were given the same dose of normal saline. After that, the mice were gavaged every day until the end of the experiment. The diet, coat color, mental state, respiration, weight changes and death of the mice were observed and recorded daily. Under ethical conditions, mice were considered dead when their weight dropped by more than 20% compared with before infection.

[0090] like Figure 7 The results showed that compared with the model group, oral administration of batrysoline could significantly inhibit the weight loss of infected mice and alleviate clinical symptoms ( Figure 7 a); Compared with the model group, the batryticatine-administered group could significantly inhibit the lung damage caused by H1N1 virus ( Figure 7 b) It shows that batroxoline has a significant protective effect on mice infected with influenza virus.

[0091] In summary, the research of the present invention proves that batroxoline has the function of inhibiting viral proliferation, and confirms that batroxoline has a strong anti-multiple viral effect at the cellular level and animal level, and can be used to prepare new broad-spectrum anti-viral infectious disease drugs, thereby providing a new way and means for the prevention and treatment of multiple viral infectious diseases, which has important research and development value and development significance.

[0092] The number of modules and processing scales described here are used to simplify the description of the present invention. Modifications and variations of the broad-spectrum antiviral drug, its pharmaceutical composition and application of the present invention are obvious to those skilled in the art.

[0093] Although the embodiments of the present invention have been disclosed as above, they are not limited to the applications listed in the specification and the implementation modes, and they can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to the specific details and the illustrations shown and described herein.

Claims

1. Use of daurisoline or its salt in the preparation of a drug for preventing and / or treating viral infectious diseases, characterized in that: The virus is one or more of adenovirus ADV and encephalomyocarditis virus EMCV.

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