CN108721281A - New antiviral drugs and its application - Google Patents
New antiviral drugs and its application Download PDFInfo
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- CN108721281A CN108721281A CN201710261806.XA CN201710261806A CN108721281A CN 108721281 A CN108721281 A CN 108721281A CN 201710261806 A CN201710261806 A CN 201710261806A CN 108721281 A CN108721281 A CN 108721281A
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- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- 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
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses leflunomide, teriflunomide, that and its derivatives of cloth quinoline in treatment virus, the especially application in the drug of picornavirus infection.The RNA virus includes but not limited to：Influenza virus, respiratory syncytial virus (RSV), hand-foot-and-mouth disease malicious (EV71), dengue fever virus (2 type dengue fever virus), zika virus, japanese encephalitis virus.These drugs have wide spectrum and excellent antiviral activity and it is relatively low to the toxicity of normal cell.
Description
Technical field
The present invention relates to medicinal chemistry arts；Specifically, leflunomide of the present invention, teriflunomide, cloth quinoline that and its spread out
Biology is preparing treatment virus, such as the drug of picornavirus infection and in treatment virus, such as answering in picornavirus infection
With.
Background technology
Disease caused by acute viral infection is the important threat of public health security, these viruses include not only well known
Influenza virus (avian influenza virus), hand-foot-and-mouth disease poison, dengue fever virus, further include some it is new hair burst novel potent virus such as
A variety of RNA virus such as Ebola virus, coronavirus.Disease caused by acute viral infection all has some common features：1)
The course of disease is short (1-2 weeks), develops fast (being rapidly developed in several after the onset days)；2) it is easy to cause severe or even dead in people at highest risk
It dies；3) crowd's propagation is easily caused；4) viral quick copy would generally cause excessive inflammatory response.
By taking influenza virus as an example, according to the data that U.S. CDC counts, the adult being hospitalized by influenza virus infection is dead
Rate is in 5%-10%, and there are about 20,000 people to die of influenza infection every year.This is not caused also including flu outbreak famous several times
Millions of death, and epidemic situation that the avian influenza virus of such as H7N9, H5N1, H5N6 even including H1N1 causes.
At 14 days or so, critically ill patient state of an illness in several days after the onset deteriorated up to dead rapidly the course of disease of influenza infection, though
It has so also given specificity antivirus drug such as Tamiflu etc. to be treated, but since morbidity later stage virus concentration is excessively high, has inhibited effect
Fruit is limited, can not save life.
Currently, antiviral drugs with target virus functional protein based on, that is, for each virus need research and develop needle
To the drug of property.It is long-term a large amount of using often although this antiviral drugs can reach very high specificity and selectivity
It will appear drug resistance.Different drugs is developed for different virus, the R&D cycle is long, and cost is also high.
Organism of the virus as parasitic life, it is necessary to which the resource for relying on host cell is bred.Therefore, this field is anxious
The small-molecule drug for the host cell design that virus is depended on for existence need to be directed to obtain broad-spectrum antiviral medicament.
Invention content
The purpose of the present invention is to provide have wide spectrum and the drug of excellent antiviral activity；These drugs are to normal thin
The toxicity of born of the same parents is relatively low；To establish material base to grind exploitation antiviral drugs of new generation.
In a first aspect, the present invention offer compound, its derivative or its pharmaceutically acceptable salt selected from the group below exist
Prepare the purposes in the drug of viral infection resisting：
In a particular embodiment, the virus is RNA virus.
In a particular embodiment, the RNA virus includes but not limited to：Influenza virus, respiratory syncytial virus (RSV),
Hand-foot-and-mouth disease poison (EV71), dengue fever virus (2 type dengue fever virus), zika virus, japanese encephalitis virus.
In second aspect, the present invention provides a kind of pharmaceutical composition, and described pharmaceutical composition includes chemical combination selected from the group below
Object, its derivative or its pharmaceutically acceptable salt and other antiviral drugs：
In a particular embodiment, other antiviral drugs are Oseltamivirs, Ribavirin, zanamivir, reach
It is one or more in luxuriant and rich with fragrance, La Ni meter Wei and Peramivir；It is preferred that Oseltamivir.
In a particular embodiment, also include pharmaceutically acceptable carrier or excipient in described pharmaceutical composition.
In the third aspect, the present invention provides a kind of method for treating virus infection, and the method includes will be selected from the group below
Pharmaceutical composition described in compound, its derivative or its pharmaceutically acceptable salt or second aspect of the present invention, which is given, to be needed
The object for the treatment of virus infection：
In a particular embodiment, the virus is RNA virus；Preferably, the RNA virus includes but not limited to：
Influenza virus, respiratory syncytial virus (RSV), hand-foot-and-mouth disease malicious (EV71), dengue fever virus (2 type dengue fever virus), stockaded village's card disease
Poison, japanese encephalitis virus.
It should be understood that within the scope of the present invention, above-mentioned each technical characteristic of the invention and have in below (eg embodiment)
It can be combined with each other between each technical characteristic of body description, to form a new or preferred technical solution.As space is limited, exist
This no longer tires out one by one states.
Specific implementation mode
Inventor after extensive and in-depth study, it was unexpectedly found that existing drug leflunomide, teriflunomide, cloth
Quinoline has wide spectrum and excellent antiviral activity, while these compounds have lower toxicity.It completes on this basis
The present invention.
Leflunomide, teriflunomide and cloth quinoline that
Existing drug leflunomide (leflunomide), teriflunomide (teriflunomide, A771726) and Bu Kuina
(brequinar) treatment rheumatoid arthritis, lupus erythematosus, a variety of primary and secondary glomerulus disease are used clinically for
Disease, prevention graft rejection reaction.Teriflunomide is effective metabolin of leflunomide, and therefore, leflunomide can be regarded as spy
The prodrug of vertical fluorine amine.Bu Kuina also has been enter into the II clinical trial phase stages, but is limited to it and treats window narrows.These have drug
There is not been reported in terms of inhibiting virus.
Inventors have surprisingly discovered that leflunomide, teriflunomide, cloth quinoline that shown in zoopery it is excellent
Different antiviral activity, therefore these have drugs except known activity is further equipped with wide spectrum and excellent antiviral
Activity.
Virus
Virus as described herein can be RNA virus (RNA virus).RNA virus is one kind of biological virus, they
Inhereditary material is made of (RNA ribonucleic acid) ribonucleic acid, and usual nucleic acid is single-stranded (ssRNA single-
Stranded RNA), also have (the dsRNA double-stranded RNA) of double-strand.
In a particular embodiment, RNA virus as described herein includes but not limited to：Influenza virus, respiratory syncystial
Precursor virus, hand-foot-and-mouth disease malicious (EV71), dengue fever virus (2 type dengue fever virus), zika virus, japanese encephalitis virus.Excellent
In the embodiment of choosing, the influenza virus includes but not limited to：H3N2 influenza viruses, H1N1 influenza viruses, H7N9 influenza diseases
Poison.
On the basis of above compound, the present invention further provides one kind for treating virus, especially RNA virus sense
The pharmaceutical composition of dye, the composition contain the compounds of this invention or its pharmaceutically acceptable salt of therapeutically effective amount, and
Pharmaceutically acceptable carrier or excipient.
The example of the pharmaceutically acceptable salt of the compounds of this invention includes but not limited to inorganic and acylate, such as salt
Hydrochlorate, hydrobromate, sulfate, citrate, lactate, tartrate, maleate, fumarate, mandelate and grass
Hydrochlorate；And it is formed with alkali such as sodium hydroxyl, three (hydroxymethyl) aminomethanes (TRIS, amine butantriol) and N-METHYL-ALPHA-L-GLUCOSAMINE
Inorganic and organic alkali salt.
Although each Man's Demands are different, those skilled in the art can determine that each in pharmaceutical composition of the present invention is lived
The optimal dose of property ingredient.Under normal circumstances, the compound of the present invention or its pharmaceutically acceptable salt, it is daily to mammal
Oral medication, dose is according to about 0.0025 to 50 mg kg of body weight.It is preferred that about 0.01 to 10 milli of per kilogram oral medication
Gram.For example, unit oral doses may include about 0.01 to 50 milligrams, preferably about 0.1 to 10 milligrams of the compounds of this invention.
Unit dose can be given one or many, be daily one or more pieces, and every contains about 0.1 to 50 milligrams, and eligibly about 0.25
To 10 milligrams of the compounds of this invention or its solvate.
The pharmaceutical composition of the present invention can be formulated into the dosage form of suitable various administration routes, including but not limited to quilt
It is configured to for parenteral, subcutaneously, vein, muscle is intraperitoneal, transdermal, and oral cavity is intrathecal, encephalic, nasal cavity or topical route administration
Form, for treating tumour and other diseases.Dosage is to effectively improve or eliminate the dose of one or more illnesss.For
The treatment of specified disease, effective quantity are the doses for being enough to improve or in some manner mitigate symptom related with disease.It is such
Dose can be used as single dose application, or can be administered according to effective therapeutic scheme.Dosage also permits healing disease, still
It is administered typically to the symptom for improving disease.Repetitively administered is generally required to realize that required symptom improves.The dosage of medicine will
According to the age of patient, health and weight, the type of concurrent treatment, the frequency for the treatment of and required treatment benefit determine.
The pharmaceutical preparation of the present invention can give any mammal, as long as they can obtain the treatment of the compounds of this invention
Effect.The most importantly mankind in these mammals.The compound of the present invention or its pharmaceutical composition can be used for treating
Ulcerative colitis.
The pharmaceutical preparation of the present invention can manufacture in a known manner.For example, by traditional mixing, granulation, ingot processed, dissolving,
Or freezing dry process manufacture.When manufacturing oral preparation, in combination with solid adjuvant material and reactive compound, selective ground and mixed
Object.After if necessary or appropriate amount of addition agent being added when necessary, granulate mixture is processed, obtains tablet or pastille core.
Suitable auxiliary material especially filler, such as carbohydrate such as lactose or sucrose, mannitol or sorbierite；Cellulose preparation or
Calcium phosphate, such as tricalcium phosphate or calcium monohydrogen phosphate；And binder, such as gelatinized corn starch, including cornstarch, wheaten starch,
Rice starch, potato starch, gelatin, tragacanth, methylcellulose, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, or
Polyvinylpyrrolidone.If desired, can increase disintegrant, than starch as mentioned above and carboxymethyl starch, crosslinking is poly-
Vinylpyrrolidone, agar or alginic acid or its salt, such as sodium alginate.Adjuvant especially flowing regulator and lubricant, example
Such as, silica, talcum, stearates, such as magnesium calcium stearate, stearic acid or polyethylene glycol.If desired, Ke Yi Give pastille cores
The suitable coating of gastric juice can be resisted by providing.For this purpose, concentration saccharide solution can be applied.Such solution can contain Arabic tree
Glue, talcum, polyvinylpyrrolidone, polyethylene glycol and/or titanium dioxide paint solution and suitable organic solvent or solvent mixing
Object.In order to prepare the coating of resistant to gastric juice, cellulose solution appropriate, such as cellulose acetate phthalic acid or hydroxypropyl can be used
Ylmethyl cellulose phthalic acid.Dyestuff or pigment can be added to the coating of tablet or pastille core.For example, for identification or
In order to characterize the combination of active constituent dosage.
In further research, inventors have surprisingly discovered that, leflunomide, teriflunomide or cloth quinoline that and its
Its antiviral drugs, such as Oseltamivir combination can generate more preferably therapeutic effect.Therefore, the present invention also provides a kind of medicines
Compositions, described pharmaceutical composition include the derivative of leflunomide, teriflunomide or cloth quinoline that or they or pharmaceutically may be used
The salt of receiving and other antiviral drugs, such as Oseltamivir, Ribavirin, zanamivir, Tamiflu, La Ni meter Wei or para rice
One or more combinations and pharmaceutically acceptable carrier or excipient in Wei.In a preferred embodiment, described
Pharmaceutical composition include that or their derivative or pharmaceutically acceptable salt of leflunomide, teriflunomide or cloth quinoline with it is difficult to understand
The combination of Si Tawei.
Therefore, the present invention also provides a kind of method for treating virus, especially picornavirus infection, this method includes giving
Need to treat the object of virus infection with the leflunomide of therapeutically effective amount, teriflunomide or cloth quinoline that or their derivative
Or the pharmaceutical composition of pharmaceutically acceptable salt or the present invention.
Medication includes but not limited to various medications well known in the art, can be subject to according to the actual conditions of patient
It determines.These methods are including but not limited to parenteral, subcutaneous, vein, muscle, intraperitoneal, transdermal, oral cavity, intrathecal, encephalic, nasal cavity
Or topical route administration.
The present invention also includes leflunomide, teriflunomide or cloth quinoline that or their derivative or pharmaceutically acceptable
Salt is preparing treatment virus, the especially purposes in the drug of picornavirus infection.
In addition, common knowledge and present disclosure of the those skilled in the art based on this field could be aware that, the present invention
The drug being related to energy forming salt or ester due to carboxyl contained therein, and then prodrug can be formed.
Advantages of the present invention
1. having wide spectrum and a drug of excellent antiviral activity present invention firstly discovers that a series of；
2. these drugs are relatively low to the toxicity of normal cell；
3. these drugs, which are research and development antiviral drugs of new generation, has established material base, critically important to have
Learning value and realistic meaning.
Technical scheme of the present invention is further described below in conjunction with specific implementation case, but following embodiment is not constituted pair
The limitation of the present invention, the various method of administration that all principles and technological means according to the present invention use, belongs to model of the present invention
It encloses.
In the following examples, the experimental methods for specific conditions are not specified, usually according to normal condition, or according to manufacturer
Proposed condition.Unless otherwise stated, otherwise percentage and number are calculated by weight.
Materials and methods
Material：
Leflunomide, teriflunomide, cloth quinoline are commercially available, 98% or more purity.
Method：
Drug IC50The measurement of (half inhibitory concentration)：Mdck cell either Vero cells or
RD cells are spread to 96 orifice plates, cultivate that grow to 90% or more after 12h spare.2 times of serial dilutions (1 × 10 of drug-1To 1
×10-10).MDCK cell monolayers suck training liquid, and PBS is washed one time, corresponding 50 μ l of dilution drug solution are added per hole, while every
The virus liquid 50ul containing 100 times of TCID50 is added in hole, and each dilution does four multiple holes.37 DEG C, 5%CO2Culture 3-5 days
Afterwards, the generation of observation CPE (cytopathy) records the positive hole that cell can be protected not generate CPE in four multiple holes and cannot protect
Protect cell generate CPE negative hole number, find out can inhibit half cell generate lesion drug dilution multiple, according to by
Reed and Muench formula calculate the IC of the drug50。
Drug TC50The measurement of (half toxicity concentration)：Mdck cell either Vero cells or RD
Cell is spread to 96 orifice plates, cultivates that grow to 90% or more after 12h spare.Drug with 2 times of serial dilutions (1 × 10-1 to 1 ×
10-10).MDCK cell monolayers suck training liquid, and PBS is washed one time, and corresponding 100 μ l of dilution drug solution are added per hole, each dilute
Degree of releasing does four multiple holes.37 DEG C, after 5%CO2 is cultivated 3-5 days, cell death caused by drug toxicity is observed, records four multiple holes
The number in the middle positive hole and the negative hole that cell death does not occur that cell death occurs, finds out the medicine for leading to half cell death
Object extension rate, according to the TC for calculating the drug by Reed and Muench formula50。
The present inventor has detected cytopathy caused by the compounds of this invention infects virus on mammalian cell
The inhibition of (cytopathic effect, CPE).
1. activity rating of embodiment
The activity test of cellular level suppressing virus replication
Such as above " materials and methods " part test the compounds of this invention of the present inventor inhibits each disease in cellular level
The activity that poison replicates.
Half-inhibition concentration IC of the compounds of this invention to H3N2 (influenza virus) in host cell MDCK50With drug half
The toxic concentration TC of number50
| Compound | IC50(uM) | TC50(uM) | SI(TC50/IC50) |
| Leflunomide | 18 | >50 | >2.8 |
| Teriflunomide | 2.5 | >50 | >25 |
| Cloth quinoline that | 1 | >50 | >50 |
Compound presses down halves of the RSV (human respiratory syncytial virus) in host cell Vero (African green monkey kidney cell)
Concentration IC processed50With the toxic concentration TC of drug half50
| Compound | IC50(uM) | TC50(uM) | SI(TC50/IC50) |
| Leflunomide | >25 | 46 | <1.84 |
| Teriflunomide | 8.25 | 39 | 4.73 |
| Cloth quinoline that | 5.36 | 31 | 5.78 |
Compound to EV71 (human hand foot Aphthovirus) host cell RD (the pernicious embryo's rhabdomyoma cell of people) half
Inhibition concentration IC50With the toxic concentration TC of drug half50
| Compound | IC50(uM) | TC50(uM) | SI(TC50/IC50) |
| Leflunomide | >25 | 35 | <1.4 |
| Teriflunomide | 9.23 | 29 | 3.14 |
| Cloth quinoline that | 4.28 | 29 | 6.78 |
Compound is to Dengue Virus 2 (dengue type 2 virus) the half of host cell Vero (African green monkey kidney cell)
Number inhibition concentration IC50With the toxic concentration TC of drug half50
| Compound | IC50(uM) | TC50(uM) | SI(TC50/IC50) |
| Leflunomide | 20 | 46 | 2.3 |
| Teriflunomide | 8.26 | 39 | 4.72 |
| Cloth quinoline that | 5.36 | 31 | 5.78 |
Compound inhibits Zika Vrius (zika virus) in the half of host cell Vero (African green monkey kidney cell)
Concentration IC50With the toxic concentration TC of drug half50
| Compound | IC50(uM) | TC50(uM) | SI(TC50/IC50) |
| Leflunomide | 20 | 46 | 2.3 |
| Teriflunomide | 2.36 | 39 | 16.5 |
| Cloth quinoline that | 0.35 | 31 | 88.6 |
Compound to JEV (japanese encephalitis virus) host cell Vero (African green monkey kidney cell) half-inhibition concentration
IC50With the toxic concentration TC of drug half50
| Compound number | IC50(uM) | TC50(uM) | SI(TC50/IC50) |
| Leflunomide | 23 | 46 | 2 |
| Teriflunomide | 3.35 | 39 | 11.6 |
| Cloth quinoline that | 1.12 | 31 | 27.7 |
The combination of embodiment 2. and other antiviral drugs
The present inventor further tests other antiviral agents of that and the prior art of leflunomide, teriflunomide, cloth quinoline
Object, Oseltamivir, Ribavirin, zanamivir, Tamiflu, La Ni meter Wei or Peramivir combination situation.
As a result, it has been found that leflunomide, teriflunomide, cloth quinoline that combination can be generated and more preferably be controlled with these antiviral drugs
Therapeutic effect；Wherein with Oseltamivir associated with therapeutic effect it is opposite preferable.
It discusses：
It is verified by In vitro cell experiment and internal mouse challenge viral dosage, the compound of the present invention has preferable anti-current
The ability of the acute infections viruses such as Influenza Virus, anti-hand-foot-and-mouth-disease poison, anti-dengue virus, with existing antiviral drugs, example
The survival rate of H7N9 severe infection mouse can be improved 25% after being combined such as Oseltamivir.With exploitation at broad-spectrum antiviral medicament
Foreground.
All references mentioned in the present invention is incorporated herein by reference, independent just as each document
It is incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art can
To be made various changes or modifications to the present invention, such equivalent forms equally fall within model defined by the application the appended claims
It encloses.
Claims (8)
1. compound selected from the group below, its derivative or its pharmaceutically acceptable salt are in the drug for preparing viral infection resisting
Purposes：
2. purposes as described in claim 1, which is characterized in that the virus is RNA virus.
3. purposes as claimed in claim 2, which is characterized in that the RNA virus includes but not limited to：Influenza virus, breathing
Road syncytial virus, hand-foot-and-mouth disease malicious (EV71), dengue fever virus (2 type dengue fever virus), zika virus, encephalitis B disease
Poison.
4. a kind of pharmaceutical composition, described pharmaceutical composition include compound selected from the group below, its derivative or its pharmaceutically may be used
The salt of receiving and other antiviral drugs：
5. pharmaceutical composition as claimed in claim 4, which is characterized in that other antiviral drugs are Oseltamivir, profit
It is one or more in Ba Weilin, zanamivir, Tamiflu, La Ni meter Wei and Peramivir；It is preferred that Oseltamivir.
6. pharmaceutical composition as described in claim 4 or 5, which is characterized in that also include pharmaceutically in described pharmaceutical composition
Acceptable carrier or excipient.
7. a kind of method for treating virus infection, the method includes by compound selected from the group below, its derivative or its pharmacy
Pharmaceutical composition described in upper any one of acceptable salt or claim 4-6 gives the object for needing to treat virus infection：
8. the method for claim 7, which is characterized in that the virus is RNA virus；Preferably, the RNA virus packet
It includes but is not limited to：Influenza virus, respiratory syncytial virus (RSV), hand-foot-and-mouth disease malicious (EV71), dengue fever virus (2 type Dengue pyreticosis
Poison), zika virus, japanese encephalitis virus.
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| CN109675042B (en) * | 2019-02-01 | 2021-03-23 | 山西锦波生物医药股份有限公司 | Compositions, methods and uses for treating and/or preventing influenza |
| CN109675042A (en) * | 2019-02-01 | 2019-04-26 | 山西锦波生物医药股份有限公司 | For treating and/or the composition of flu-prevention, method and purposes |
| CN109864989B (en) * | 2019-03-08 | 2021-07-23 | 中国农业科学院兰州兽医研究所 | Application of brequinar in preparation of drugs for preventing foot-and-mouth disease virus infection |
| CN109864989A (en) * | 2019-03-08 | 2019-06-11 | 中国农业科学院兰州兽医研究所 | A kind of that application in the drug of preparation prevention mouth disease virus infection of cloth quinoline |
| CN109758447B (en) * | 2019-03-11 | 2021-06-08 | 中国农业科学院兰州兽医研究所 | Application of teriflunomide in preparation of drugs for preventing foot-and-mouth disease virus infection |
| CN109758447A (en) * | 2019-03-11 | 2019-05-17 | 中国农业科学院兰州兽医研究所 | A kind of application of teriflunomide in the drug of preparation prevention mouth disease virus infection |
| WO2021164672A1 (en) * | 2020-02-18 | 2021-08-26 | 华东理工大学 | Anti-rna virus drug and application thereof |
| CN113456632A (en) * | 2020-02-18 | 2021-10-01 | 华东理工大学 | anti-RNA virus medicine and application thereof |
| CN113456632B (en) * | 2020-02-18 | 2023-09-26 | 华东理工大学 | anti-RNA virus medicine and its application |
| CN113456637A (en) * | 2020-03-30 | 2021-10-01 | 华东理工大学 | Quinoline derivative of anti-RNA virus medicine and application thereof |
| CN113456817A (en) * | 2020-03-30 | 2021-10-01 | 华东理工大学 | DHODH inhibitor of anti-RNA virus medicine and application thereof |
| CN113456637B (en) * | 2020-03-30 | 2024-03-01 | 华东理工大学 | Quinoline derivative of anti-RNA virus drug and application thereof |
| CN113456817B (en) * | 2020-03-30 | 2024-05-10 | 华东理工大学 | DHODH inhibitor of anti-RNA virus drug and application thereof |
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