CN117547596A - Application of human blood apolipoprotein A1 product in preparation of anti-enveloped virus medicine - Google Patents
Application of human blood apolipoprotein A1 product in preparation of anti-enveloped virus medicine Download PDFInfo
- Publication number
- CN117547596A CN117547596A CN202311550067.8A CN202311550067A CN117547596A CN 117547596 A CN117547596 A CN 117547596A CN 202311550067 A CN202311550067 A CN 202311550067A CN 117547596 A CN117547596 A CN 117547596A
- Authority
- CN
- China
- Prior art keywords
- virus
- apolipoprotein
- human
- mug
- product
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
-
- 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)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Marine Sciences & Fisheries (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides an application of a human apolipoprotein A1 product in preparing an anti-enveloped virus medicament, belonging to the technical field of biological medicines. Experiments prove that the human apolipoprotein A1 product has strong inhibition and killing effects on envelope viruses such as HIV (human immunodeficiency Virus) and the like. When the concentration of the human blood apolipoprotein A1 is 6.09 mug/mL, 12.18 mug/mL, 24.36 mug/mL, 48.72 mug/mL, 97.44 mug/mL, 194.88 mug/mL and 389.76 mug/mL, the inhibition rate of the human blood apolipoprotein A1 to HIV virus is 53.3%, 65.8%, 74.1%, 80.8%, 82.5%, 90.8% and 95.0%, which shows that the human blood apolipoprotein A1 product has strong inhibition and killing effect to HIV and provides a new thought for developing anti-enveloped virus drugs.
Description
Technical Field
The invention relates to the technical field of biological medicine, in particular to application of a human apolipoprotein A1 product in preparation of an anti-enveloped virus medicine.
Background
Viruses are a major pathogenic organism which can invade host cells and threaten human health and carry genetic information, the virus structure is generally formed by jointly packaging nucleic acid components consisting of DNA or RNA and a capsid structure which is wrapped on the outer layer, and some common DNA viruses reported at present are herpes viruses, hepatitis B viruses, human papillomaviruses, adenoviruses, poxviruses and the like, when the viruses infect cells, the DNA of the viruses is released into host cytoplasm, and the components can be identified by specific receptors in the host cells so as to start antiviral immune response of the organism.
Apolipoprotein A1 is a major subtype of proteins in plasma, a major constituent of high density lipoproteins, and is a clinically usual detection index. Apolipoprotein A1 is synthesized in the small intestine and liver, and in small amounts in the kidneys and gonads, degraded by the kidneys. The main function of the apolipoprotein A1 is to activate lecithin-cholesterol acyltransferase, transport superfluous cholesterol in tissues to liver for treatment, and have the effects of removing tissue lipid and resisting atherosclerosis. The apolipoprotein A1 has clear clinical significance and the highest concentration in tissues, so the apolipoprotein A1 becomes a common clinical detection index. The reference value of the apolipoprotein A1 is 1.0-1.6 g/L. Apolipoprotein A1 directly reflects plasma high density lipoprotein levels and is inversely related to the incidence of coronary heart disease. Thus, apolipoprotein A1 is one of the more sensitive indicators for diagnosing coronary heart disease. Elevated apolipoprotein A1 is also seen in chronic hepatitis, prolonged overdrinking, pregnancy status, administration of certain drugs (e.g. antiepileptic drugs, contraceptives, estrogens, etc.). The decrease of apolipoprotein A1 is found in atherosclerosis (especially in the case of the obstructive), diabetes, liver dysfunction, luteinizing hormone application, etc. However, the use of apolipoprotein A1 for anti-enveloped viruses has not been reported.
Disclosure of Invention
The invention aims to provide an application of a human apolipoprotein A1 product in preparing an anti-enveloped virus medicament.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides application of a human apolipoprotein A1 product in preparation of an anti-enveloped virus medicament.
Preferably, the viruses include HIV virus, COVID-19 virus and other enveloped viruses.
Preferably, the viruses further include herpes simplex virus, measles virus, pseudorabies virus, chicken pox virus, monkey immunodeficiency virus and influenza virus.
Preferably, the medicament is in the form of intravenous drops.
Preferably, the human apolipoprotein A1 preparation is used at a concentration of 6 to 400. Mu.g/mL.
By adopting the technical scheme, the invention has the following beneficial effects: the invention has proved by experiments that the human blood apolipoprotein A1 product has inhibiting and killing effects on HIV virus and other enveloped viruses, when the concentration of human blood apolipoprotein A1 is 6.09 mug/mL, 12.18 mug/mL, 24.36 mug/mL, 48.72 mug/mL, 97.44 mug/mL, 194.88 mug/mL and 389.76 mug/mL, the inhibiting rate on HIV virus is 53.3%, 65.8%, 74.1%, 80.8%, 82.5%, 90.8% and 95.0%, respectively, thus the human blood apolipoprotein A1 has obvious inhibiting effects on the viruses, and provides a new idea for developing antiviral drugs.
Drawings
FIG. 1 is a bar graph showing the inhibition of HIV virus by human apolipoprotein A1 preparations at various concentrations.
Detailed Description
The invention provides application of human apolipoprotein A1 in preparation of anti-enveloped virus medicaments. The concentration of human apolipoprotein A1 used is 6 to 400. Mu.g/mL, more preferably 100 to 300. Mu.g/mL, still more preferably 200. Mu.g/mL. The viruses include HIV virus, COVID-19 virus, herpes simplex virus, measles virus, pseudorabies virus, chicken pox virus, monkey immunodeficiency virus and influenza virus.
The enveloped virus has a layer of envelope, the viral envelope, which is enclosed outside a protein capsid, and which is synthesized mainly by the substance and energy of the host cell and also contains the glycoprotein of the virus itself. The viral envelope is antigenic and aids in the entry of the virus into the host cell and maintains the structural integrity of the virion. When viruses invade host cells, glycoprotein on the surface of the envelope recognizes and binds to host cell surface receptors, the viral envelope binds to host cell membranes, and finally the viral capsid and viral genome enter the host cells, completing the infection process. The antiviral mechanism of the human apolipoprotein A1 product is that the human apolipoprotein A1 product can destroy the envelope of viruses to kill the viruses.
Human apolipoprotein A1 preparations act only on enveloped viruses and not on the cell membranes of higher animals, including humans. This is because cholesterol in the higher animal cell membrane prevents the hydrophobic surface of the human apolipoprotein A1 product from inserting into the phospholipid bilayer, and because of the difference in the membrane-outer structure of the microorganism and the higher animal cell membrane: the sialic acid on the outer surface of the membrane of higher animals is 80 angstroms from the membrane and may bind to the positively charged region of the antimicrobial peptide preventing it from killing in close proximity to the cell membrane. Human apolipoprotein A1 can interact with the surface of a target biological film, and depending on the positive and negative electrical effects of the two, the biophysical properties of the film are changed, so that viruses are killed.
The human apolipoprotein A1 preparation of the present invention can be extracted from plasma by salting-out.
The discovery process comprises the following steps: plasma viral inactivation is the physical or chemical disruption of the viral protein structure, which allows viruses that may be present in the plasma to lose their ability to infect, cause disease and reproduce. At present, the virus is usually killed by inactivation for 10min at 60 ℃, but plasma proteins are denatured under the temperature condition, so that a plasma protectant is required to be added. When 1000 parts of plasma are inactivated, the inventor adds the human blood apolipoprotein A1 product as a protective agent, and surprisingly discovers that the human blood apolipoprotein A1 product has a killing effect on enveloped viruses.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
The human apolipoprotein A1 preparation used in the examples of the present invention was prepared by salting out. HIV-1/IIIB virus was purchased from MCE life sciences reagent service and MT-4 cells were purchased from Wankel Biotech Co.
EXAMPLE 1WST-1 assay for determining the inhibition of HIV-1/IIIB Virus by human apolipoprotein A1
Inhibition ofThe rate measurement was performed in a P3 biosafety cabinet, MT-4 cells cultured to the logarithmic growth phase were collected, the total number of cells and the number of living cells were counted, and the cell concentration was adjusted to 1X 10 with RPMI1640 medium containing 10% FBS 5 cel1/mL; 100 mu L of cell suspension is taken and added into a 96-well plate, 100TCID50 HIV-1/IIIB virus (50 mu L/well) is added, and pre-diluted human serum apolipoprotein A1 samples (50 mu L/well) with different concentrations are added, so that the final concentrations are 6.09 mu g/mL, 12.18 mu g/mL, 24.36 mu g/mL, 48.72 mu g/mL, 97.44 mu g/mL, 194.88 mu g/mL and 389.76 mu g/mL respectively, 4 compound wells are arranged in parallel for each sample, and 4 compound wells are respectively arranged for blank control, cell control, virus control and positive control (AZT, 60 nmol/L); at 37 ℃,5% CO 2 After 96h incubation in an incubator, 10. Mu.L/well of WST-1 (5 mmol/L) solution was added, incubated at 37℃for 4h, and absorbance was measured at 450 nm.
The calculation formula is as follows: inhibition Ratio (IR) = (As-Av)/(Ac-Av)
As: the average value of the absorbance values of the samples;
av: the mean value of absorbance values of the virus control group;
ac: mean absorbance of cell control group;
the measurement results show that the inhibition rate of 60nmol/LAZT to HIV-1/IIIB virus is 71%, and the inhibition rate of different concentrations of human apolipoprotein A1 to HIV-1/IIIB virus is shown in figure 1. As shown in FIG. 1, human serum apolipoprotein A1 can effectively inhibit HIV-1/IIIB virus, and the inhibition rate of human serum apolipoprotein A1 products on HIV-1/IIIB virus is 53.3%, 65.8%, 74.1%, 80.8%, 82.5%, 90.8% and 95.0% respectively at the concentration of 6.09 μg/mL, 12.18 μg/mL, 24.36 μg/mL, 48.72 μg/mL, 97.44 μg/mL, 194.88 μg/mL and 389.76 μg/mL; the inhibition rate of the human apolipoprotein A1 concentration is 24.36 mu g/mL, which is equivalent to that of the positive medicine AZT of 60 nmol/L.
From the above examples, the present invention provides the application of human apolipoprotein A1 in preparing anti-enveloped virus medicine, and human apolipoprotein A1 can inhibit and kill enveloped virus effectively.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (5)
1. The application of human blood apolipoprotein A1 product in preparing medicine for resisting enveloped virus.
2. The use according to claim 1, wherein the enveloped viruses comprise HIV virus and covd-19 virus.
3. The use according to claim 1, wherein the enveloped viruses further comprise herpes simplex virus, measles virus, pseudorabies virus, chicken pox virus, monkey immunodeficiency virus and influenza virus.
4. The use according to claim 1, wherein the medicament is in the form of intravenous drops.
5. The use according to claim 1, wherein the human apolipoprotein A1 is used at a concentration of 6 to 400 μg/mL.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311550067.8A CN117547596A (en) | 2023-11-20 | 2023-11-20 | Application of human blood apolipoprotein A1 product in preparation of anti-enveloped virus medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311550067.8A CN117547596A (en) | 2023-11-20 | 2023-11-20 | Application of human blood apolipoprotein A1 product in preparation of anti-enveloped virus medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117547596A true CN117547596A (en) | 2024-02-13 |
Family
ID=89814368
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311550067.8A Pending CN117547596A (en) | 2023-11-20 | 2023-11-20 | Application of human blood apolipoprotein A1 product in preparation of anti-enveloped virus medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117547596A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1830488A (en) * | 2005-11-23 | 2006-09-13 | 杨宝田 | High density lipoprotein and its lipoprotein carrier used as anti coated virus medicine |
| US20090048171A1 (en) * | 2003-12-24 | 2009-02-19 | Curtis Dobson | Treatment of viral infections |
| CN110590937A (en) * | 2018-06-13 | 2019-12-20 | 杨宝田 | Preparation method and application of human apolipoprotein A1 product |
| EP3916389A1 (en) * | 2020-05-27 | 2021-12-01 | Biopredictive | Method of diagnosis of infection by the sars-cov-2 virus |
-
2023
- 2023-11-20 CN CN202311550067.8A patent/CN117547596A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090048171A1 (en) * | 2003-12-24 | 2009-02-19 | Curtis Dobson | Treatment of viral infections |
| CN1830488A (en) * | 2005-11-23 | 2006-09-13 | 杨宝田 | High density lipoprotein and its lipoprotein carrier used as anti coated virus medicine |
| CN110590937A (en) * | 2018-06-13 | 2019-12-20 | 杨宝田 | Preparation method and application of human apolipoprotein A1 product |
| EP3916389A1 (en) * | 2020-05-27 | 2021-12-01 | Biopredictive | Method of diagnosis of infection by the sars-cov-2 virus |
Non-Patent Citations (4)
| Title |
|---|
| B J OWENS等: "Apolipoprotein A-I and its amphipathic helix peptide analogues inhibit human immunodeficiency virus-induced syncytium formation", 《J CLIN INVEST》, vol. 86, no. 4, 31 October 1990 (1990-10-31), pages 1142 - 1150, XP002343094, DOI: 10.1172/JCI114819 * |
| R V SRINIVAS 等: "Antiviral effects of apolipoprotein A-I and its synthetic amphipathic peptide analogs", 《VIROLOGY》, vol. 176, no. 1, 31 May 1990 (1990-05-31), pages 48 - 57, XP023051174, DOI: 10.1016/0042-6822(90)90229-K * |
| 胡国芳，陈保生，杨晓慧，王树蕙: "血浆载脂蛋白A－Ⅰ生理功能的研究──A－Ⅰ及其裂解片段对单纯疱疹病毒感染细胞的作用", 中国医学科学院学报, no. 02, 30 April 1994 (1994-04-30), pages 1 - 6 * |
| 陈保生: "载脂蛋白的结构和功能与病毒病的预防和治疗", 《中国医学科学院学报 》, vol. 29, no. 3, 30 July 2007 (2007-07-30), pages 448 - 451 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gendelman et al. | Slow, persistent replication of lentiviruses: role of tissue macrophages and macrophage precursors in bone marrow. | |
| Bergmann et al. | Antigens of hepatitis delta virus in the liver and serum of humans and animals | |
| JP2001500160A (en) | Protein / lipid vesicles and autologous vaccines containing the vesicles | |
| Pauza et al. | Human immunodeficiency virus infection of monoblastoid cells: cellular differentiation determines the pattern of virus replication | |
| AU735708B2 (en) | Supression of cyclin kinase 2 activity for prevention and treatment of DNA viral infections | |
| EP1420065A1 (en) | Process for producing inactivated virus envelope | |
| Scheule | Novel preparation of functional Sindbis virosomes | |
| CN107699591A (en) | A kind of knockout PD 1 T cell preparation method and applications | |
| EP0294443B1 (en) | Use of nucleosides for the manufacture of medicament for treatment of diseases caused by retrovirus or hepatitis b virus | |
| CN117547596A (en) | Application of human blood apolipoprotein A1 product in preparation of anti-enveloped virus medicine | |
| EP0974347B1 (en) | Antiviral agents | |
| US20020155132A1 (en) | Method for treatment of immunodeficiency virus infection | |
| CZ295765B6 (en) | Therapeutical preparation exhibiting virucidal activity | |
| Bergamini et al. | A tetrazolium-based colorimetric assay for quantification of HIV-1-induced cytopathogenicity in monocyte-macrophages exposed to macrophage-colony-stimulating factor | |
| JPH06504429A (en) | Inhibition of viral replication | |
| WO1997037661A1 (en) | Preventive and remedy for viral infections | |
| CN113018421B (en) | Use of cholesterol-25-hydroxylase and its enzymatic product in the preparation of drugs for inhibiting novel coronavirus | |
| Barmak et al. | Altered cellular responses to interferon induction by poly I· poly C: Priming and hyporesponsiveness in cells treated with interferon preparations | |
| JP4014330B2 (en) | Viral infection protection agent | |
| US20100016244A1 (en) | D-glucopyranose 1-[3,5-bis (1,1-dimethylethy)-4-hydroxybenzoate] and its derivatives, preparation and use thereof | |
| CN112957361B (en) | Application of trametinib in the preparation of anti-arenavirus antiviral preparations | |
| CN120919097A (en) | Application of lactic acid and interferon in preparing antiviral medicine | |
| Henke et al. | The Envelope Protein of SARS-CoV-2 Inhibits Viral Protein Synthesis and Infectivity of Human Immunodeficiency Virus type 1 (HIV-1) | |
| CA2437168A1 (en) | Retinoid hepatitis therapy | |
| CN120114452A (en) | A drug for preventing mycobacterium tuberculosis infection |
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 |