CN117503742A - Application of Endosidin-2 in preparation of antiviral drugs - Google Patents

Application of Endosidin-2 in preparation of antiviral drugs Download PDF

Info

Publication number
CN117503742A
CN117503742A CN202311487171.7A CN202311487171A CN117503742A CN 117503742 A CN117503742 A CN 117503742A CN 202311487171 A CN202311487171 A CN 202311487171A CN 117503742 A CN117503742 A CN 117503742A
Authority
CN
China
Prior art keywords
virus
endosidin
preparation
bovine
pharmaceutical composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202311487171.7A
Other languages
Chinese (zh)
Inventor
王洪梅
马文青
何洪彬
和鲁腾
何畅
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shandong Normal University
Original Assignee
Shandong Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shandong Normal University filed Critical Shandong Normal University
Priority to CN202311487171.7A priority Critical patent/CN117503742A/en
Publication of CN117503742A publication Critical patent/CN117503742A/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of Endosidin-2 in preparation of antiviral drugs. The invention discovers that the compound Endosidin-2 can effectively inhibit the replication of various viruses including vesicular stomatitis virus, herpes simplex virus type I, bovine herpes virus type I and bovine parainfluenza 3 virus, blocks the release of the viruses, has relatively smaller toxicity to cells, and has the prospect of developing medicaments for resisting the viruses, thereby opening up new medicinal uses for Endosidin-2, laying an experimental foundation for developing high-efficiency specific antiviral medicaments and providing a new field of view, and has good practical application value.

Description

Application of Endosidin-2 in preparation of antiviral drugs
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of Endosidin-2 in preparation of antiviral drugs.
Background
The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art.
Viruses are parasitic in host cells and must replicate, transcribe, and translate within the host cell as non-cellular organisms. Infectious diseases caused by viral infection have the characteristics of various kinds, strong infectivity, high morbidity, high mortality rate and the like, and seriously endanger the life health of human beings and animals. The research and development of the viral disease medicine is a difficulty and a hot spot of the research and development of the global medicine, the research and development of safe and effective medicine and the development of new antiviral application of the existing medicine, provide reference for the research and development of more efficient antiviral medicine, and have important significance for pushing the research and development of antiviral medicine.
The application of the micromolecular medicine Endosidin-2 (called ES2 for short, CAS: 1839524-44-5) in cancers and diabetes mellitus discovers that the ES2 can improve the clinical chemotherapy curative effect of cisplatin on epithelial ovarian cancer and can also be used for treating type 2 diabetes mellitus. Therefore, ES2 is expected to be a target drug for treating diabetes, cancer and other human diseases, but the antiviral effect of ES2 is not clear.
Disclosure of Invention
In order to overcome the defects in the prior art, the inventor provides application of Endosidin-2 in preparing antiviral drugs through long-term technical and practical exploration. The invention discovers and proves that the Endosidin-2 has the functions of resisting vesicular stomatitis virus, herpes simplex virus I, bovine herpes virus I, bovine parainfluenza 3 virus and the like for the first time through researches, so the invention has the prospect of developing antiviral drugs. Based on the above results, the present invention has been completed.
In order to achieve the technical purpose, the invention adopts the following technical scheme:
in a first aspect of the invention there is provided the use of Endosidin-2 for the preparation of an antiviral product; wherein the virus comprises at least one of vesicular stomatitis virus, herpes simplex virus type I, bovine herpes virus type I and bovine parainfluenza 3 virus. And thus Endosidin-2 is effective in preventing and/or treating diseases associated with the above viruses.
In a second aspect of the invention, a pharmaceutical composition is provided, which is composed of Endosidin-2 and at least one other pharmaceutically active ingredient and/or at least one other non-pharmaceutically active ingredient.
In a third aspect of the present invention, there is provided a method for preventing and/or treating a disease associated with the above-mentioned viral infection, the method comprising administering to a subject the above-mentioned Endosidin-2 or the above-mentioned pharmaceutical composition.
Compared with the prior art, the one or more technical schemes have the following beneficial effects:
the technical scheme discovers that the compound Endosidin-2 can effectively inhibit the replication of various viruses including vesicular stomatitis virus, herpes simplex virus type I, bovine herpes virus type I and bovine parainfluenza type 3 virus, blocks the release of the viruses, has relatively small toxicity to cells, has the prospect of developing medicaments for resisting the viruses, opens up new medicinal uses for Endosidin-2, lays an experimental foundation for developing high-efficiency specific antiviral medicaments and provides a new field of view, and therefore has good practical application value.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention.
FIG. 1 shows CC50 of Endosidin-2 in HeLa cells, vero cells and MDBK cells in an example of the invention.
FIG. 2 shows IC50 values of Endosidin-2 acting on VSV, HSV-1, boHV-1 and BPIV3 viruses in examples of the present invention.
FIG. 3 shows SI values of Endosidin-2 acting on VSV, HSV-1, boHV-1 and BPIV3 viruses in examples of the present invention.
FIG. 4 shows the effect of Endosidin-2 on inhibiting the replication of VSV, HSV-1, boHV-1 and BPIV3 in the examples of the invention.
Detailed Description
It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the present application. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments in accordance with the present application. As used herein, the singular is also intended to include the plural unless the context clearly indicates otherwise, and furthermore, it is to be understood that the terms "comprises" and/or "comprising" when used in this specification are taken to specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.
As mentioned above, there has been no found application of Endosidin-2 in antiviral applications.
In view of this, in one exemplary embodiment of the present invention, endosidin-2 is used in the manufacture of an antiviral product. Wherein the virus comprises at least one of vesicular stomatitis virus, herpes simplex virus type I, bovine herpes virus type I and bovine parainfluenza 3 virus. And thus, endosidin-2 is effective for preventing and/or treating the above virus-related diseases.
It should be noted that this application is disclosed for the first time and is not the same as the known application.
The antiviral properties are at least expressed as the ability to directly inactivate the above viruses and/or inhibit replication of the above viruses.
The product may be a drug or a test agent for use in basic research and thus may be used to construct relevant cells or animal models.
Thus, in a further embodiment of the present invention, there is provided:
(a) Use of Endosidin-2 for the preparation of a virus-inactivated product;
(b) Use of Endosidin-2 for the preparation of a product for inhibiting viral replication.
Wherein the virus comprises at least one of vesicular stomatitis virus, herpes simplex virus type I, bovine herpes virus type I and bovine parainfluenza 3 virus.
According to the present invention, not only is the use of endo-2 in the preparation of antiviral drugs disclosed, but also the use of endo-2 in combination with at least one other pharmaceutically active ingredient is disclosed, which enhances this effect. Endosidin-2 may also be used in combination with other non-pharmaceutically active ingredients, in place of or in addition to other pharmaceutically active ingredients.
In yet another embodiment of the present invention, a pharmaceutical composition is provided, which is composed of Endosidin-2 and at least one other pharmaceutically active ingredient and/or at least one other non-pharmaceutically active ingredient.
The other pharmaceutically active ingredients include substances having the effect of inhibiting and/or killing the above viruses.
The non-pharmaceutically active ingredient comprises a pharmaceutically acceptable carrier, excipient and/or diluent.
In yet another embodiment of the present invention, the non-pharmaceutically active ingredient comprises:
pharmaceutically compatible inorganic or organic acids or bases, polymers, block copolymers, monosaccharides, polysaccharides, ionic and nonionic surfactants or lipids;
pharmacologically harmless salts, flavoring agents, vitamins, antioxidants, stabilizers and/or preservatives.
The administration form of the pharmaceutical composition includes: liquid dosage forms, solid dosage forms, external preparations and sprays;
in yet another embodiment of the invention, the following dosage forms are included: true solutions, colloids, microparticle dosage forms, emulsion dosage forms, mixed rotation dosage forms, tablets, capsules, dripping pills, aerosols, pills, powders, solutions, suspensions, emulsions, granules, suppositories, freeze-dried powder injection, inclusion compounds, landfill agents, patches and liniment.
In yet another embodiment of the present invention, there is provided a method for preventing and/or treating a disease associated with the above virus, comprising administering to a subject the above therapeutically effective dose of Endosidin-2 or the above pharmaceutical composition.
The virus comprises at least one of vesicular stomatitis virus, herpes simplex virus type I, bovine herpes virus type I and bovine parainfluenza type 3 virus,
the subject refers to an animal, preferably a mammal, more preferably a ruminant, such as a cow, which has been the subject of treatment, observation or experiment. "therapeutically effective dose" refers to the amount that results in improvement of any parameter or clinical symptom. The actual dosage may vary from subject to subject and does not necessarily refer to the total amount that eliminates all disease symptoms, and may be determined using methods well known in the art and will not be described in detail herein.
The invention is further illustrated by the following examples, which are given for the purpose of illustration only and are not intended to be limiting. Any simple modification, equivalent variation and modification of the implementation mode according to the technical substance of the invention are all within the scope of the technical proposal of the invention.
Examples
1. Material
Hela cells, vero cells, MDBK cells, MDCK cells, and Vesicular Stomatitis Virus (VSV), herpes simplex virus type I (HSV-1), bovine herpes virus type I (BoHV-1), bovine parainfluenza 3 virus (BPIV 3) were all maintained by ruminant disease research centers at the university of Shandong.
ES2 is purchased from sparkjade; DMSO was purchased from Solarbio; cell culture reagents such as DMEM medium, PBS, fetal bovine serum, etc. were purchased from BI company.
2. Method and results
Cytotoxicity detection of 2.1ES2
The CCK-8 kit was used for the cytotoxic effect of ES2 on HeLa cells, vero cells, and MDBK cells. Dispersing the above cells by pancreatin digestion, counting, inoculating 100 μl cell suspension into 96-well culture plate, and inoculating 5×10 5 Individual cells/wells. 37 ℃ 5% CO 2 Culturing in a cell incubator for 12-24h, observing that the cell has good adhesion and suckingThe culture medium of each well was prepared by adding DMEM medium containing different concentrations of ES2 to the experimental group, adding the medium without ES2 to the blank group, and then adding 5% CO to the 96-well plate at 37 ℃to the experimental group 2 Incubate in incubator for 48h. Directly adding 10 μl of CCK-8 solution into each well, adding 5% CO at 37deg.C 2 Incubate in incubator for 1h. Taking out the 96-well plate, detecting the OD value of each well at the wavelength of 450nm by using an enzyme-labeled instrument, analyzing and processing data, and calculating the cell survival rate: cell viability% = (dosed cell OD/control cell OD) ×100%. The drug concentration (CC 50) at T/c=50% was determined and the proliferation curve was plotted.
The results showed that the CC50 of ES2 in HeLa cells, vero cells and MDBK cells was 163.6. Mu.M, 582.8. Mu.M and 314.6. Mu.M, respectively (FIG. 1).
2.2ES2 antiviral ability detection
Hela cells, vero cells and MDBK cells were passaged separately into 96-well plates and inoculated with VSV, HSV-1, BPIV3 and BoHV-1 (0.001 MOI/well), 5% CO at 37℃respectively 2 Incubating for 1h in a cell incubator, adding cell maintenance solution containing 2% serum of ES2 with different concentrations, continuously observing for 4-7 days, and calculating IC50 and SI value of ES2 acting on virus.
The results showed that the IC50 of ES2 acting on VSV, HSV-1, boHV-1 and BPIV3 were 73.7. Mu.M, 142.3. Mu.M, 66.82. Mu.M and 91.24. Mu.M, respectively (FIG. 2). SI values were all greater than 1, indicating the potential of ES2 against the four viruses described above (fig. 3).
2.3ES2 inhibiting viral replication
Hela cells, vero cells and MDBK cells were passaged separately into 6-well plates, after confluence with monolayers, VSV, HSV-1, boHV-1 and BPIV3 (0.1 MOI/well) were inoculated separately, 5% CO at 37deg.C 2 Incubating in a cell incubator for 1h, adding cell maintenance solution containing 2% serum of ES2 and DMSO respectively, harvesting virus after 24h, and measuring TCID of virus solution 50 。
The results are shown in FIG. 4, where the virus titers of VSV, HSV-1, boHV-1 and BPIV3 were significantly reduced after ES2 treatment compared to the control DMSO-treated group, indicating that ES2 inhibited replication of VSV, HSV-1, boHV-1 and BPIV 3.
The foregoing description is only of the preferred embodiments of the present application and is not intended to limit the same, but rather, various modifications and variations may be made by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims (10)

  1. Use of endosidin-2 for the preparation of an antiviral product; wherein the virus comprises at least one of vesicular stomatitis virus, herpes simplex virus type I, bovine herpes virus type I and bovine parainfluenza 3 virus.
  2. 2. The use according to claim 1, wherein said antiviral properties are at least expressed as an ability to inactivate viruses and/or inhibit viral replication.
  3. 3. The use according to claim 1, wherein the product is a pharmaceutical or test agent for use in basic research.
  4. Use of endosidin-2 for the preparation of a product for inactivating a virus.
  5. Use of endosidin-2 for the preparation of a product for inhibiting viral replication.
  6. 6. The use according to claim 4 or 5, wherein the virus comprises at least one of vesicular stomatitis virus, herpes simplex virus type I, bovine herpes virus type I and bovine parainfluenza type 3 virus.
  7. 7. A pharmaceutical composition, characterized in that it consists of Endosidin-2 and at least one other pharmaceutically active ingredient and/or at least one other non-pharmaceutically active ingredient.
  8. 8. The pharmaceutical composition according to claim 7, wherein the other pharmaceutically active ingredient comprises a substance having the effect of inhibiting and/or killing the virus.
  9. 9. The pharmaceutical composition of claim 7, wherein the non-pharmaceutically active ingredient comprises a pharmaceutically acceptable carrier, excipient, and/or diluent.
  10. 10. The pharmaceutical composition of claim 7, wherein the pharmaceutical composition is administered in a form comprising: liquid dosage forms, solid dosage forms, external preparations and sprays.
CN202311487171.7A 2023-11-08 2023-11-08 Application of Endosidin-2 in preparation of antiviral drugs Pending CN117503742A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202311487171.7A CN117503742A (en) 2023-11-08 2023-11-08 Application of Endosidin-2 in preparation of antiviral drugs

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202311487171.7A CN117503742A (en) 2023-11-08 2023-11-08 Application of Endosidin-2 in preparation of antiviral drugs

Publications (1)

Publication Number Publication Date
CN117503742A true CN117503742A (en) 2024-02-06

Family

ID=89745034

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202311487171.7A Pending CN117503742A (en) 2023-11-08 2023-11-08 Application of Endosidin-2 in preparation of antiviral drugs

Country Status (1)

Country Link
CN (1) CN117503742A (en)

Similar Documents

Publication Publication Date Title
CN112451517A (en) Application of epigallocatechin 3-O- (3-O-methyl) gallate in preparing anti-coronavirus medicine
CN101264083A (en) Compositions and methods for preventing and treating mucositis and weight loss
WO1996009764A1 (en) Method, compositions, and apparatus for treating and preventing respiratory viral infections
Lampis et al. Enhancement of anti-herpetic activity of glycyrrhizic acid by physiological proteins
CN108434167A (en) Application of the different corilagin in preparing anti-influenza virus medicament
CN114748458A (en) Application of propranolol in resisting coronavirus infection
CN107961239B (en) Triple pharmaceutical composition and application thereof in treating gastroenteritis
CN112707874A (en) Antiviral compound and preparation method thereof
CN117503742A (en) Application of Endosidin-2 in preparation of antiviral drugs
CN115844879B (en) Application of melatonin in resisting Gattavirus
CA2465062C (en) Preventive and/or therapeutic agent for viral infection
CA2412676A1 (en) Anti-viral composition
CN113274375A (en) Application of metformin and derivatives or pharmaceutically acceptable salts thereof in preparation of drugs for treating coronavirus infection
CN109793729A (en) The purposes of Nifuroxazide or its salt in treatment osteosarcoma
CN114377027A (en) Application of pulsatilla saponin B4 in preparation of medicine for treating or preventing SARS-CoV-2
EP0255420B1 (en) Antiviral agent for inhibiting growth of virus of acquired immune deficiency syndrome (aids)
CN115337308B (en) Application of ACSS2 inhibitor in preparation of anti-H1N 1 subtype swine influenza virus drugs
CN116098916B (en) Application of Ma Liba-virus in preparing anti-H13 subtype AIV (air-induced respiratory tract) drugs
CN105055387A (en) Applications of taurine in preparing medicines for resisting viruses
CN111904998B (en) Oral cavity spray agent with targeting, slow-release and film-forming functions for inhibiting virus or bacteria and preparation method thereof
TWI803229B (en) Compound tsyi-zac is used to inhibit dengue virus infection and its medicinal use
CN108670965A (en) Application of the teriflunomide in preparing anti-west nile virus drug
CN107648249B (en) Application of the desgalactotigonin in the drug for preparing prevention influenza infection
CN116270647A (en) Application of rilpivirine in preparation of anti-H1N 1 subtype swine influenza virus drugs
CN112386600B (en) Application of Hupeimine in preparation of medicine for preventing acute kidney injury

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination