CN-121971443-A - Coptisine hydrochloride inhibits HAdV and RSV infection by stabilizing the viral G-quadruplex structure

CN121971443ACN 121971443 ACN121971443 ACN 121971443ACN-121971443-A

Abstract

The invention relates to coptisine hydrochloride for inhibiting HAdV and RSV infection by stabilizing a virus G-quadruplex structure, and particularly provides application of coptisine or pharmaceutically acceptable salt thereof for inhibiting hAdV, even simultaneously inhibiting hAdV and RSV.

Inventors

CHEN XINWEN
YANG QI
ZHONG JIAYI
ZHOU ANQI
TANG JIELIN
ZHOU YUAN

Assignees

广州国家实验室

Dates

Publication Date: 20260505
Application Date: 20260330

Claims (11)

1. Use of coptisine or a pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride) in the manufacture of a medicament for the treatment and/or prophylaxis of human adenovirus (hAdV) infection or a disease caused thereby.
2. The use of claim 1, wherein the disease caused by infection with human adenovirus (hAdV) comprises respiratory disease, ocular disease, digestive tract disease, cystitis or meningitis, etc.; preferably, the respiratory diseases comprise common cold, pharyngitis, bronchitis, pneumonia and the like; Preferably, the ocular diseases include epidemic keratoconjunctivitis and the like; preferably, the digestive tract diseases include gastroenteritis and the like.
3. Use of coptisine or a pharmaceutically acceptable salt thereof, preferably coptisine hydrochloride, for the manufacture of a medicament for the treatment and/or prophylaxis of co-infection of human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV) or a disease caused thereby.
4. The use of claim 3, wherein the diseases caused by co-infection of human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV) include respiratory diseases, ocular diseases, digestive diseases, cystitis, meningitis, etc.; preferably, the respiratory diseases comprise common cold, pharyngitis, bronchitis, pneumonia and the like; Preferably, the ocular diseases include epidemic keratoconjunctivitis and the like; preferably, the digestive tract diseases include gastroenteritis and the like.
5. The application of coptisine or pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride) in preparing medicaments for resisting human adenovirus (hAdV) is provided.
6. Use of coptisine or a pharmaceutically acceptable salt thereof, preferably coptisine hydrochloride, in the preparation of a medicament against human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV).
7. Use of coptisine or a pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride) in the preparation of an agent for inhibiting replication or proliferation of human adenovirus (hAdV); Preferably, the coptisine or a pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride) inhibits replication or proliferation of human adenovirus (hAdV) by stabilizing the viral G-quadruplex structure.
8. Use of coptisine or a pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride) in the preparation of an agent for inhibiting replication or proliferation of human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV); Preferably, the coptisine or a pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride) inhibits replication or proliferation of human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV) by stabilizing the viral G-quadruplex structure.
9. The use of any one of claims 1-8, wherein the pharmaceutically acceptable salt is a hydrochloride, phosphate, hydrogen phosphate, sulfate, bisulfate, sulfite, acetate, oxalate, malonate, valerate, glutamate, oleate, stearate, laurate, p-toluenesulfonate, methanesulfonate, fumarate, isethionate, maleate, malate, tartrate, citrate, benzoate, pamoate, salicylate, vanillate, or succinate.
10. The use of any one of claims 1-6 and 9, wherein the medicament further has one or more features selected from the following (i) - (viii): (i) The medicament further comprises one or more pharmaceutically acceptable carriers, diluents and/or excipients; Preferably, the carrier comprises one or more of ion exchangers, alumina, aluminium stearate, lecithin, serum proteins (such as human serum albumin), buffer substances (such as phosphates), glycerol, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts, electrolytes, protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulosic substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, beeswax, lanolin; Preferably, the diluent comprises one or more of microcrystalline cellulose, lactose, starch, hydroxypropyl cellulose, sucrose, glucose, sorbitol, sodium chloride, calcium sulfate, and calcium carbonate; Preferably, the excipient comprises one or more of binders (e.g. polyvinylpyrrolidone, starch slurry, gelatin), disintegrants (e.g. crospovidone, sodium carboxymethyl starch, low substituted hydroxypropylcellulose), lubricants (e.g. talc, hydrogenated vegetable oil, polyethylene glycol), glidants (e.g. micro powder silica gel), coating materials (e.g. opadry, cellulose acetate phthalate), solvents/co-solvents (e.g. water for injection, ethanol, propylene glycol), preservatives (e.g. sodium benzoate, hydroxyphenyl esters), antioxidants (e.g. sodium bisulphite, ascorbic acid, tocopherol), flavouring/colouring agents (e.g. aspartame, peppermint essence, titanium dioxide, food colour); (ii) The medicament is presented in the form of an oral dosage form; (iii) The medicine is presented in the form of a traditional Chinese medicine preparation or a Chinese patent medicine preparation; (iv) The drug is administered in an amount of 0.1-1000mg (calculated as active ingredient); (v) The unit dose of the medicine contains 0.1-1000mg of coptisine or pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride); (vi) The frequency of administration of the medicament is once a day, twice a day, three times a day, once every other day, once a week, twice a week, once a three weeks or once a four week; (vii) In the medicine, the weight ratio of coptisine or the pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride) is 1-99%; (viii) The medicament is used in combination with one or more additional therapeutic agents including cidofovir, brinzdofovir, ribavirin, palivizumab, nixie Wei Shankang, pan Wei Xishan antibodies.
11. The use of any one of claims 1-10, wherein: The human adenovirus (hAdV) is a B or C type human adenovirus (hAdV); preferably, the human adenovirus (hAdV) is a human adenovirus of type B3, C1, C2 or C5 (hAdV); Or the Respiratory Syncytial Virus (RSV) is a type a or B Respiratory Syncytial Virus (RSV); Preferably, the Respiratory Syncytial Virus (RSV) is A2, ON1, B9320 or B18537 Respiratory Syncytial Virus (RSV).

Description

Coptisine hydrochloride inhibits HAdV and RSV infection by stabilizing the viral G-quadruplex structure Technical Field The invention belongs to the field of medicines, and particularly relates to coptisine hydrochloride for inhibiting HAdV and RSV infection by stabilizing a virus G-quadruplex structure. Background Human adenovirus (hAdV) is a non-enveloped, double-stranded DNA virus with a large genome and a wide range of cell and tissue tropism. It is mainly spread by the spray, contact or faeces-mouth route, and is a common pathogen causing respiratory tract infection (such as common cold and pneumonia), conjunctivitis, gastroenteritis and the like of children and adults. Respiratory Syncytial Virus (RSV) is an enveloped single-stranded RNA virus belonging to the pneumoviridae family. It is the primary viral pathogen that causes lower respiratory tract infections (such as bronchiolitis and pneumonia) in infants, the elderly and immunocompromised individuals. RSV is transmitted primarily by spray and contact, and infections are a significant seasonal and global public health concern. Further, the co-circulation of human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV) will result in severe co-infection and exacerbation of the disease. Therefore, the development of anti-human adenovirus (hAdV) drugs, even drugs against both human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV), is of great importance. Disclosure of Invention Aiming at the problems in the prior art, the inventor discovers that coptisine or pharmaceutically acceptable salt thereof (especially coptisine hydrochloride) can effectively inhibit hAdV, even inhibit hAdV and RSV simultaneously, has excellent antiviral effect, is obviously superior to ribavirin Lin Huoxi dofovir and the like in the prior art, and has excellent application prospect. In particular, in a first aspect, the present invention provides the use of coptisine or a pharmaceutically acceptable salt thereof, preferably coptisine hydrochloride, in the manufacture of a medicament for the treatment and/or prophylaxis of human adenovirus (hAdV) infection or a disease caused thereby. Meanwhile, the invention also provides coptisine or pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride), which is used for treating and/or preventing human adenovirus (hAdV) infection or diseases caused by the human adenovirus. Also, the present invention provides a method for treating and/or preventing human adenovirus (hAdV) infection or a disease caused by it, comprising administering to a subject in need thereof an effective amount of coptisine or a pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride). In some embodiments, the disease caused by infection with human adenovirus (hAdV) comprises a respiratory disease, an ocular disease, a digestive disease, cystitis, meningitis, or the like. In some embodiments, the respiratory disease includes common cold, pharyngitis, bronchitis, pneumonia, or the like. In some embodiments, the ocular disease comprises epidemic keratoconjunctivitis, and the like. In some embodiments, the digestive tract disease includes gastroenteritis and the like. In a second aspect, the present invention provides the use of coptisine or a pharmaceutically acceptable salt thereof, preferably coptisine hydrochloride, in the manufacture of a medicament for the treatment and/or prophylaxis of co-infection of human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV) or a disease caused thereby. At the same time, the invention also provides coptisine or pharmaceutically acceptable salt thereof (preferably coptisine hydrochloride), which is used for treating and/or preventing human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV) co-infection or diseases caused by the same. Also, the present invention provides a method for treating and/or preventing human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV) co-infection or a disease caused thereby, comprising administering to a subject in need thereof an effective amount of coptisine or a pharmaceutically acceptable salt thereof, preferably coptisine hydrochloride. In some embodiments, the disease caused by co-infection of human adenovirus (hAdV) and Respiratory Syncytial Virus (RSV) includes respiratory disease, ocular disease, digestive disease, cystitis, meningitis, or the like. In some embodiments, the respiratory disease includes common cold, pharyngitis, bronchitis, pneumonia, or the like. In some embodiments, the ocular disease comprises epidemic keratoconjunctivitis, and the like. In some embodiments, the digestive tract disease includes gastroenteritis and the like. In a third aspect, the present invention provides the use of coptisine or a pharmaceutically acceptable salt thereof, preferably coptisine hydrochloride, for the preparation of an anti-human adenovirus (hAdV) medicament. At the same time, the invention also provides coptisine or pharmaceut