CN-122005557-A - Application of veratramine in preparing lysosome trapping inhibiting preparation and antiviral preparation

Abstract

The invention relates to the technical field of biological medicines, in particular to application of veratramine in preparing a preparation for inhibiting lysosome capture and an antiviral preparation. The invention discovers that veratramine can be captured by lysosomes and accumulated in the lysosomes, and can be used for preparing preparations for inhibiting the capture of the lysosomes. Veratramine has the characteristics of small toxic and side effects and high safety, and is obviously superior to the existing lysosome capture inhibitors such as chloroquine and the like.

Inventors

• TIAN NANNAN
• WANG JINCHENG
• YANG CHAOXU
• HUANG LEYI
• WENG QINJIE

Assignees

• 浙江大学台州研究院

Dates

Publication Date

20260512

Application Date

20251230

Claims (10)

1. 1. Use of veratramine in the preparation of a preparation for inhibiting lysosomal capture.
2. 2. The use according to claim 1, wherein the lysosome is a lysosome in a tumor cell.
3. 3. The use according to claim 2, wherein the tumor cell is at least one of a liver cancer cell, a colorectal adenocarcinoma cell, a gastric adenocarcinoma cell, an ovarian adenocarcinoma cell, a breast cancer cell, a cervical cancer cell, and a neuroblastoma cell.
4. 4. The use of claim 3, wherein the hepatoma cells are HepG2 cells, the colorectal adenocarcinoma cells are HCT-8 cells, the gastric adenocarcinoma cells are MGC-803 cells, the ovarian adenocarcinoma cells are SK-OV-3 cells, the breast cancer cells are MCF-7 cells, the cervical cancer cells are HeLa cells, and the neuroblastoma cells are SH-SY5Y cells.
5. 5. The use according to claim 1, wherein veratramine is veratramine or a pharmaceutically acceptable salt thereof, which is a salt of veratramine with hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid or citric acid.
6. 6. The use according to claim 1, wherein the formulation is a scientific or pharmaceutical agent.
7. 7. Use of veratramine in the preparation of an antiviral agent, said virus being an enveloped virus.
8. 8. The use of claim 7, wherein veratramine acts on lysosomes and inhibits fusion of the viral envelope with the cell membrane.
9. 9. The use according to claim 7, wherein the enveloped virus is SARS coronavirus or ebola virus.
10. 10. The use of claim 7, wherein the antiviral agent comprises veratramine and at least one other antiviral agent.

Description

Application of veratramine in preparing lysosome trapping inhibiting preparation and antiviral preparation Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of veratramine in preparing a preparation for inhibiting lysosome capture and antiviral preparation. Background The development of broad-spectrum and high-efficiency antiviral drugs has been the direction of scientific research efforts to seriously threaten global public health safety. Virus invasion of cells is a critical initial step in the infection cycle, where many enveloped viruses (e.g., SARS coronavirus, ebola virus, etc.) rely on the endocytic-lysosomal pathway of the cell to complete the infection. After such viruses enter cells by endocytosis, the acidic environment of lysosomes and specific hydrolases are required to complete fusion of the viral envelope with the cell membrane, uncoating and release of the viral genome. Therefore, lysosomes have become a target for antiviral drugs of great interest, and can effectively block the infection process of such viruses by inhibiting the function of lysosomes. Currently, the drugs used to study or attempt to use as lysosomal inhibitors are mainly chloroquine (Chloroquine) and hydroxychloroquine (Hydroxychloroquine). They are weak base drugs capable of destroying the internal environment necessary for viral replication by neutralizing the acidic pH of lysosomes and show a certain antiviral potential in preclinical studies. However, chloroquine and hydroxychloroquine have the problems of limited efficacy, high dosage required for effect and serious side effects such as retinal toxicity, cardiac toxicity and the like possibly caused by long-term or large-dosage use, and the wide clinical application of chloroquine and hydroxychloroquine is greatly limited. Thus, there is an urgent need for safer and more effective lysosomal inhibitors for use against enveloped viruses. Disclosure of Invention Aiming at the technical problems, the invention provides a novel lysosome capturing inhibiting compound and related application thereof. Specifically, the invention unexpectedly discovers that veratramine can specifically target lysosomes of cells, is captured and enriched by the lysosomes, can competitively inhibit the lysosomes from capturing other alkaline compounds (such as chloroquine, alkaline anticancer drugs and the like), and further provides application of veratramine in preparation of lysosome capturing preparations. In addition, veratramine (chemical structure shown in figure 1) has antiviral activity and can be used for preparing antiviral preparations. This is probably because, after the virus enters the cell by endocytosis, it is necessary to rely on the acidic environment of lysosomes and specific hydrolases to accomplish fusion of the viral envelope with the cell membrane, uncoating and release of the viral genome. After veratramine is dissolved by lysosomes, the acid environment of the lysosomes is changed, so that the function of the lysosomes is affected, and viruses are further inhibited from entering cells, and the antiviral effect is achieved. Compared with the prior art, the application of veratramine in preparing the preparation for inhibiting lysosome capture and antiviral preparation has at least one of the following beneficial effects that a novel compound for inhibiting lysosome capture is provided, the veratramine has small toxic and side effects and high safety, the problems of high toxicity, narrow treatment window and the like of the traditional chloroquine and the like are effectively solved, and after acting on the lysosome, the veratramine has antiviral activity, can be used for preparing the antiviral preparation, can be used in combination with other antiviral medicines, and has better curative effect. Drawings FIG. 1 is a chemical structure diagram of veratramine (vetramine) of the present invention; FIG. 2 shows the concentration of veratramine captured by lysosomes in the experimental group and the inhibitor control group according to the first embodiment of the present invention; FIG. 3 is a concentration-dependent curve of veratramine capture in HepG2 cells according to example one of the present invention. Detailed Description Various exemplary embodiments of the invention will now be described in detail, which should not be considered as limiting the invention, but rather as more detailed descriptions of certain aspects, features and embodiments of the invention. Unless otherwise defined, 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 invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification