WO2022270656A1 - Composition pour la prévention ou le traitement d'une infection par le virus nipah comprenant des nanoparticules d'or en tant que principe actif - Google Patents
Composition pour la prévention ou le traitement d'une infection par le virus nipah comprenant des nanoparticules d'or en tant que principe actif Download PDFInfo
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- WO2022270656A1 WO2022270656A1 PCT/KR2021/007987 KR2021007987W WO2022270656A1 WO 2022270656 A1 WO2022270656 A1 WO 2022270656A1 KR 2021007987 W KR2021007987 W KR 2021007987W WO 2022270656 A1 WO2022270656 A1 WO 2022270656A1
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- nipah virus
- gold nanoparticles
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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
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/242—Gold; Compounds thereof
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
Definitions
- the present invention relates to a composition for preventing or treating Nipah virus comprising gold nanoparticles as an active ingredient.
- Nipah virus infection which has a fatality rate of up to 75%, as another potential pandemic risk.
- the report was published by the Pharmaceutical Accessibility Foundation (AMF), a non-profit organization supported by the British and Dutch governments.
- AMF Pharmaceutical Accessibility Foundation
- the AMF said, "Nipah virus is a new infectious disease that draws another attention, and it can spread at any time.”
- the greatest risk of Nipah virus is that "there is no cure and the mortality rate is very high,” he said, and the mortality rate would reach 40 to 75% depending on the region where it occurred.
- Nipah virus infects both humans and animals.
- Animals such as fruit bats, pigs, cats, dogs, horses, and goats can be hosts, and the average incubation period is 5 to 14 days, but it has been reported that it can increase up to 45 days.
- the virus is transmitted to humans through infected animals or contaminated food, or directly from person to person. When a person is infected, there are no symptoms or symptoms such as acute respiratory illness and fatal encephalitis appear.
- Nipah virus binds to the Ephrin B2/3 receptor of the host using G, F surface glycoproteins (glycoproteins), mainly passes through the blood-brain barrier and binds to endothelial cells of the brain blood vessels, encephalitis It is characterized by inducing. Because the Ephrin B2/3 receptor mediates viral entry and membrane-fusion into host cells, it is a major target for vaccines and therapeutics (Virology Journal Volume 7, pp305). There is no vaccine yet for this virus, and only symptomatic treatment is available.
- G F surface glycoproteins
- Nipah virus G and F glycoproteins are multifunctional molecular structures that mediate Nipah virus entry into host cells. As shown in Figure 2, it first binds to the host cell surface receptor through the G subunit. It is known that the two domains of G are truncated and induce viral attachment through conformational changes in the F glycoprotein. This F glycoprotein exists in two structurally distinct pre-fusion and post-fusion conformations.
- the present invention was made to solve the above problems, and the present inventors confirmed that gold nanoparticles can block the invasion into cells by interfering with the shape change of Nipah virus to enter host cells, and based on this Thus, the present invention was completed.
- the present invention provides a pharmaceutical composition for treating or preventing Nipah virus containing gold nanoparticles.
- the present invention provides a method for treating or preventing Nipah virus, comprising administering a composition containing gold nanoparticles to a subject.
- the present invention provides a use of a composition containing gold nanoparticles for treating or preventing Nipah virus.
- the gold nanoparticles are characterized in that the gold nanoparticles block the Nipah virus protein from invading cells by interfering with the shape change of the Nipah virus protein.
- the gold nanoparticles are characterized in that they are included in the form of a colloidal gold solution having a negative charge.
- the composition is characterized in that it further comprises an ephrin B2/3 receptor inhibitor.
- the ephrin B2/3 receptor inhibitor is salicylic acid.
- the gold nanoparticles are characterized in that they have a diameter of 0.1 to 100 nm.
- the composition according to the present invention contains gold nanoparticles as an active ingredient, and the present invention confirmed the treatment and prevention of Nipah virus by treating the gold nanoparticles.
- the gold nanoparticles may prevent Nipah virus proteins from entering cells by interfering with changes in the shape of Nipah virus proteins, thereby preventing or treating Nipah viruses.
- 1 is a schematic diagram showing the morphology of Nipah virus.
- FIG. 2 shows the structure of the Ephrin2/3 receptor.
- Figure 3 schematically shows the process in which the composition of the present invention binds to a virus and treats it.
- Salicylate-adsorbed colloid gold attacks Nipah virus crystals and destroys the nucleocapsid structure of Nipah virus.
- Nipah virus can enter cells by binding to the Ephrin B2/3 receptor of the host using G,F surface glycoproteins (glycoproteins).
- G,F surface glycoproteins glycoproteins
- Ephrin B2/3 receptors mediate viral entry and membrane-fusion into host cells.
- the present inventors confirmed that the gold nanoparticles can inhibit the cell invasion of Nipah virus by interfering with the change in the shape of the glycoprotein on the surface of Nipah virus, blocking the Nipah virus protein from entering cells, and based on this, Thus, the present invention was completed.
- the present invention provides a pharmaceutical composition for treating or preventing Nipah virus containing gold nanoparticles.
- the gold nanoparticles block the Nipah virus protein from entering cells by interfering with the shape change of the Nipah virus protein.
- Nipah virus can be treated or prevented through such blocking.
- the negatively charged colloidal gold solution can disrupt the nucleocapsid structure of the virus. Intervention of the gold nanoparticles makes it difficult for the morphological change of the F protein.
- the gold nanoparticles may be provided in the form of a colloidal gold solution having a negative charge.
- the gold colloidal solution When used orally, it can more effectively prevent virus from entering cells, but the method of administration is not limited.
- the gold nanoparticles are characterized in that they have a diameter of 0.1 to 100 nm. More preferably, it may be 0.1 to 10 nm, but is not limited thereto.
- Nipa virus a disease to be prevented or treated by the composition of the present invention, is a virus that first became prevalent in Malaysia in 1998 and caused numerous casualties. Genome and protein information related to the Nipah virus can be freely collected and used from a research information database. there is.
- prevention refers to any activity that inhibits or delays the onset of Nipah virus by administration of the pharmaceutical composition according to the present invention.
- treatment refers to all activities in which symptoms of Nipah virus are improved or beneficially changed by administration of the pharmaceutical composition according to the present invention.
- the present invention is to provide the simplest method for blocking Nipah virus RNA from entering cells by using negatively charged colloidal gold in vascular endothelial cells for oral use and interfering with protein conformational changes. At this time, a small amount of gold particles can be transported to the systemic circulation (10-40 nm).
- Nipah virus passes through the blood-brain barrier and binds to cerebrovascular cells, the negatively charged colloidal gold nanoparticles can bind to the virus, and then the virus can be removed by phagocytosis, thereby infecting the virus. can stop the progression of
- the gold nanoparticles of the present invention may be used in combination with salicylate (aspirin), an Ephrin B2/3 receptor inhibitor.
- salicylic acid, an Ephrin B2/3 receptor inhibitor, and negatively charged gold nanoparticles can be adsorbed, thereby increasing the efficacy of the Ephrin B2/3 receptor inhibitor. That is, gold nanoparticles acting as a nucleocapsid structure destroyer in the present invention are combined with an Ephrin B2/3 receptor inhibitor to inhibit the progress of Nipah virus infection.
- the Ephrin B2/3 receptor inhibitor may be aspirin, but is not limited thereto.
- the colloidal gold solution provided in the present invention refers to a colloid or suspension of sub-micrometer-sized gold particles present in a fluid, generally water.
- the pharmaceutical composition according to the present invention may include a pharmaceutically acceptable carrier in addition to the active ingredient.
- the pharmaceutically acceptable carrier is one commonly used in the formulation, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose , polyvinyl pyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil, but are not limited thereto.
- lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, and the like may be further included.
- the pharmaceutical composition of the present invention can be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically applied) depending on the desired method, and the dosage depends on the patient's condition, body weight and disease. Depending on the degree, drug form, administration route and time, it can be appropriately selected by those skilled in the art.
- the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.
- pharmaceutically effective amount means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type of patient's disease, severity, activity of the drug, It may be determined according to factors including sensitivity to the drug, administration time, route of administration and excretion rate, duration of treatment, drugs used concurrently, and other factors well known in the medical field.
- the pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art.
- the effective amount of the pharmaceutical composition of the present invention may vary depending on the patient's age, sex, condition, body weight, absorption rate, inactivation rate and excretion rate of the active ingredient in the body, type of disease, and concomitant drugs, generally 100 to 500 mg per 1 kg of body weight may be administered daily or every other day, or divided into 1 to 3 times a day. However, since it may increase or decrease depending on the administration route, severity of obesity, gender, weight, age, etc., the dosage is not limited to the scope of the present invention in any way.
- the present invention provides a method for treating or preventing Nipah virus, comprising administering a composition containing gold nanoparticles to a subject.
- "individual” means a subject in need of treatment of a disease, and more specifically, means a mammal such as a human or non-human primate, mouse, dog, cat, horse, and cow. do.
- the present invention may provide a composition containing gold nanoparticles for treating or preventing Nipah virus.
- composition of the present invention a composition containing 3-8 nm gold particles was prepared.
- the effect of the composition containing the gold nanoparticles was studied by intratracheal administration to adult female mice. As a result, the administered gold nanoparticles were found in lung macrophages already 1 hour after single injection.
- a negatively charged colloidal gold solution can access the Nipahvirus and prevent conformational changes of the G and F domains, while reaching the Nipahvirus nucleocapsid, resulting in viral attachment to the host receptor and fusion into vascular cells. It can be seen that Nipah particles that cannot be counted will be phagocytosed by macrophages.
- the composition of the present invention is a pharmaceutical composition for the treatment or prevention of Nipah virus containing gold nanoparticles, wherein when the gold nanoparticles are administered, the composition of the G, F glycoproteins of Nipah virus is inhibited, thereby preventing the Nipah virus protein from entering cells. can prevent intrusion. Accordingly, the composition can be usefully used in the field of Nipah virus treatment.
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- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne une composition pharmaceutique pour le traitement ou la prévention d'une infection par le virus Nipah comprenant des nanoparticules d'or. Selon la présente invention, les nanoparticules d'or peuvent empêcher ou traiter une infection par le virus Nipah en interférant avec le changement conformationnel de la protéine du virus Nipah et en empêchant la protéine du virus Nipah de pénétrer dans la cellule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/KR2021/007987 WO2022270656A1 (fr) | 2021-06-24 | 2021-06-24 | Composition pour la prévention ou le traitement d'une infection par le virus nipah comprenant des nanoparticules d'or en tant que principe actif |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/KR2021/007987 WO2022270656A1 (fr) | 2021-06-24 | 2021-06-24 | Composition pour la prévention ou le traitement d'une infection par le virus nipah comprenant des nanoparticules d'or en tant que principe actif |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022270656A1 true WO2022270656A1 (fr) | 2022-12-29 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2021/007987 WO2022270656A1 (fr) | 2021-06-24 | 2021-06-24 | Composition pour la prévention ou le traitement d'une infection par le virus nipah comprenant des nanoparticules d'or en tant que principe actif |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2022270656A1 (fr) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20140053906A (ko) * | 2011-05-13 | 2014-05-08 | 조에티스 엘엘씨 | 헨드라 및 니파 바이러스 ｇ 당단백질 면역원성 조성물 |
| KR102264873B1 (ko) * | 2020-01-17 | 2021-06-14 | 대한민국(질병관리청장) | 니파바이러스 g 당단백질에 특이적인 단클론 항체 및 이의 용도 |
-
2021
- 2021-06-24 WO PCT/KR2021/007987 patent/WO2022270656A1/fr active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20140053906A (ko) * | 2011-05-13 | 2014-05-08 | 조에티스 엘엘씨 | 헨드라 및 니파 바이러스 ｇ 당단백질 면역원성 조성물 |
| KR102264873B1 (ko) * | 2020-01-17 | 2021-06-14 | 대한민국(질병관리청장) | 니파바이러스 g 당단백질에 특이적인 단클론 항체 및 이의 용도 |
Non-Patent Citations (3)
| Title |
|---|
| KERRY ROUT GEORGE; MALIK SANTOSH; REDDA YISEHAK TSEGAYE; SAHOO SABUJ; PATRA JAYANTA KUMAR; MAJHI SANATAN: "Nano-based approach to combat emerging viral (NIPAH virus) infection", NANOMEDICINE: NANOTECHNOLOGY, BIOLOGY, AND MEDICINE, ELSEVIER, AMSTERDAM, NL, vol. 18, 1 January 1900 (1900-01-01), AMSTERDAM, NL, pages 196 - 220, XP085713698, ISSN: 1549-9634, DOI: 10.1016/j.nano.2019.03.004 * |
| ROBERTA NOBERINI, ILARIA LAMBERTO, ELENA B. PASQUALE: "Targeting Eph receptors with peptides and small molecules: Progress and challenges", SEMINARS IN CELL AND DEVELOPMENTAL BIOLOGY., ACADEMIC PRESS., GB, vol. 23, no. 1, 1 February 2012 (2012-02-01), GB , pages 51 - 57, XP055452706, ISSN: 1084-9521, DOI: 10.1016/j.semcdb.2011.10.023 * |
| SARAVANAN MUTHUPANDIAN; MOSTAFAVI EBRAHIM; VINCENT SAVARIAR; NEGASH HADUSH; ANDAVAR RAJAPRIYA; PERUMAL VENKATESAN; CHANDRA NAMAS; : "Nanotechnology-based approaches for emerging and re-emerging viruses: Special emphasis on COVID-19", MICROBIAL PATHOGENESIS, ACADEMIC PRESS LIMITED, NEW YORK, NY., US, vol. 156, 28 April 2021 (2021-04-28), US , XP086599062, ISSN: 0882-4010, DOI: 10.1016/j.micpath.2021.104908 * |
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