CN117159558A - Application of tripterine in preparation of Japanese encephalitis virus resistant medicament - Google Patents
Application of tripterine in preparation of Japanese encephalitis virus resistant medicament Download PDFInfo
- Publication number
- CN117159558A CN117159558A CN202210585170.5A CN202210585170A CN117159558A CN 117159558 A CN117159558 A CN 117159558A CN 202210585170 A CN202210585170 A CN 202210585170A CN 117159558 A CN117159558 A CN 117159558A
- Authority
- CN
- China
- Prior art keywords
- japanese encephalitis
- tripterine
- encephalitis virus
- ns2b
- jev
- 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
- KQJSQWZMSAGSHN-JJWQIEBTSA-N celastrol Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)[C@](C)(C(O)=O)CC[C@]1(C)CC[C@]2(C)C4=CC=C1C3=CC(=O)C(O)=C1C KQJSQWZMSAGSHN-JJWQIEBTSA-N 0.000 title claims abstract description 30
- 239000003814 drug Substances 0.000 title claims abstract description 21
- 241000710842 Japanese encephalitis virus Species 0.000 title abstract description 23
- 238000002360 preparation method Methods 0.000 title abstract description 8
- 206010014596 Encephalitis Japanese B Diseases 0.000 claims description 15
- 201000005807 Japanese encephalitis Diseases 0.000 claims description 15
- 241000700605 Viruses Species 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 10
- 239000000945 filler Substances 0.000 claims description 3
- 238000010521 absorption reaction Methods 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000003623 enhancer Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 238000002513 implantation Methods 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 238000001179 sorption measurement Methods 0.000 claims description 2
- 238000005507 spraying Methods 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 108091005804 Peptidases Proteins 0.000 abstract description 17
- 239000004365 Protease Substances 0.000 abstract description 17
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 abstract description 17
- 239000003112 inhibitor Substances 0.000 abstract description 11
- 230000005764 inhibitory process Effects 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 5
- 239000000969 carrier Substances 0.000 abstract description 3
- 108090000623 proteins and genes Proteins 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 241000710843 Japanese encephalitis virus group Species 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101710144111 Non-structural protein 3 Proteins 0.000 description 3
- 241001052560 Thallis Species 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- KQJSQWZMSAGSHN-UHFFFAOYSA-N (9beta,13alpha,14beta,20alpha)-3-hydroxy-9,13-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid Natural products CC12CCC3(C)C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C2=CC=C2C1=CC(=O)C(O)=C2C KQJSQWZMSAGSHN-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- AQKDBFWJOPNOKZ-UHFFFAOYSA-N Celastrol Natural products CC12CCC3(C)C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C2=CC=C2C1=CC(=O)C(=O)C2C AQKDBFWJOPNOKZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 206010014599 encephalitis Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 1
- 235000019750 Crude protein Nutrition 0.000 description 1
- 241000256054 Culex <genus> Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- 208000004929 Facial Paralysis Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 101800001030 Non-structural protein 2A Proteins 0.000 description 1
- 101800001020 Non-structural protein 4A Proteins 0.000 description 1
- 101800001019 Non-structural protein 4B Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000033952 Paralysis flaccid Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 101800001838 Serine protease/helicase NS3 Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 241000830536 Tripterygium wilfordii Species 0.000 description 1
- 208000036826 VIIth nerve paralysis Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108700010756 Viral Polyproteins Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000004598 abnormal eye movement Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 208000028331 flaccid paralysis Diseases 0.000 description 1
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 235000015398 thunder god vine Nutrition 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides an application of tripterine in preparation of a Japanese encephalitis virus resistant medicament, which aims at JEV NS2B-NS3 protease targets in Japanese encephalitis virus, uses the tripterine as an inhibitor of the protease, has good inhibition activity on JEV NS2B-NS3 protease in Japanese encephalitis virus, has various carriers and administration modes, and is convenient to use and easy to obtain.
Description
Technical Field
The invention belongs to the technical field of pharmacy, and particularly relates to application of tripterine in preparation of a Japanese encephalitis virus resistant medicament.
Background
Japanese encephalitis (JE, japanese encephalitis) is one of the most important epidemic and sporadic encephalitis in tropical areas of Asia. Since the first case in 1871 was found in japan, the geographical area of japanese encephalitis virus (JEV, japanese encephalitis virus) transmission has gradually increased with the development of decades until the whole asia is covered. It is estimated that 30 hundred million people live in JEV epidemic areas, including china, india and peninsula southeast asia. About 70,000 cases of human japanese encephalitis infection are reported each year, and no effective reporting system has been established in most countries with high japanese encephalitis incidence, so that the actual incidence should be higher than the statistical incidence, and thus JEV is far more harmful than what we see. The natural circulatory transmission pathway of JEV involves many vertebrate hosts, culex trilobus as a transmission medium, and pigs and birds can be considered as two more important amplification hosts. Patients with the onset of illness are manifested as blurred consciousness, fever, nausea, vomiting, headache, seizures and intracranial neurological symptoms including facial paralysis, ptosis and abnormal eye movement, and can develop flaccid paralysis, which usually affects the lower limbs, severe cases spread to the extremities, and serious sequelae such as paralysis of the extremities can be caused after illness. Since there is no specific drug against encephalitis B virus at present, the incidence rate is still high and constant under the condition that the JEV vaccination rate is continuously improved, and the JEV vaccination rate is a public health problem which needs to be faced in Asian areas. Therefore, the research on specific drugs of Japanese encephalitis virus is very important at present.
The N-terminal domain of the JEV NS3 protein and the cofactor NS2B form a protease that hydrolyzes the viral polyprotein polymer. NS2B comprises a hydrophilic region, the central region of which comprises a β -barrel which, for its stability, is folded around the β -barrel of the NS3 protease. Upon substrate binding, NS2B undergoes conformational changes, affecting the stability of the β -hairpin, making it part of the active site. Active NS2B-NS3 is necessary for hydrolytic cleavage at the junction of NS2A/NS2B, NS2B/NS3, NS3/NS4A and NS4B/NS 5. In addition, it can also act as a hub for the formation of viral replication complexes, affecting the pathogenic mechanisms of the virus and the immune response of the host. Thus, JEV NS2B-NS3 can be used as an important target for the research of Japanese encephalitis virus inhibitors.
The tripterine, the English name is Celastrol, is derived from root bark of a traditional Chinese medicine tripterygium wilfordii, is a popular natural compound in recent years, has anti-inflammatory activity in various researches, protects the central nervous system, has anti-diabetes, cardiovascular protection, anticancer and antifungal effects, and has great therapeutic potential. However, the application of tripterine in resisting Japanese encephalitis virus infection is not reported so far.
Disclosure of Invention
The invention aims at solving the problem that the tripterine is used as an inhibitor of the protease aiming at JEV NS2B-NS3 protease target spot in Japanese encephalitis virus, and provides the application of the tripterine in preparing Japanese encephalitis virus resistant medicaments.
In order to solve the technical problems, the invention adopts the following technical scheme:
the application of tripterine in preparing a Japanese encephalitis virus resistant medicament comprises the following steps of:
further, the anti-Japanese encephalitis virus medicament comprises the tripterine and one or more pharmaceutically acceptable carriers.
Further, the carrier comprises a diluent, an excipient, a filler, a binder, a wetting agent, a disintegrating agent, an absorption enhancer, a surfactant, an adsorption carrier, a lubricant and a synergist.
Further, the anti-Japanese encephalitis virus drug is selected from the group consisting of granules, powder, syrup, tablets, pills, suppositories, and combinations thereof.
Further, the mode of administration of the anti-Japanese encephalitis virus drug includes oral administration, injection, implantation, external application, spraying, inhalation or a combination thereof.
The invention provides an application of tripterine in preparation of anti-Japanese encephalitis virus medicines, which aims at JEV NS2B-NS3 protease targets in Japanese encephalitis viruses, uses the tripterine as an inhibitor of the protease, has good inhibition activity on JEV NS2B-NS3 protease in Japanese encephalitis viruses, and has various carriers and administration modes, and is convenient to use and easy to obtain.
The tripterine CAS number of the invention is 34157-83-0 and is purchased from Shanghai Tao Su Biochemical technology Co., ltd.
Drawings
FIG. 1 is a schematic illustration of the inhibitory effect of celastrol on JEV NS2B-NS3 protease of Japanese encephalitis virus according to an embodiment of the present invention;
FIG. 2 shows the inhibitory effect of tripterine on JEV NS2B-NS3 protease of Japanese encephalitis virus according to one embodiment of the present invention 50 Schematic measurement.
Detailed Description
Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to like or similar elements or elements having like or similar functions throughout. The embodiments described below by referring to the drawings are illustrative and intended to explain the present invention and should not be construed as limiting the invention.
Referring to fig. 1-2, the application of tripterine in preparing anti-japanese encephalitis virus drugs is provided in the embodiment of the invention, and the specific implementation manner is as follows:
1. expression and purification of JEV NS2B-NS3 protease;
(1) The reference constructs a recombinant pET-15B plasmid containing the gene encoding JEV NS2B-NS3pro and transformed into E.coli competent cell BL21 (DE 3).
(2) Positive monoclonal colonies were picked on plates containing ampicillin resistance, and when cultured in LB liquid medium (50 mg/L ampicillin) at 37℃until the OD600 of the bacterial liquid became about 0.6, isopropyl thiogalactoside was added to a final concentration of 0.5mM, and protein expression was induced at 16℃for 16-18 hours.
(3) Centrifuging at 3500rpm for 15min by a floor centrifuge to collect thalli, washing the precipitated thalli twice, re-suspending the thalli in a bacteria breaking buffer solution (20mM Tris,300mM NaCl,pH 7.5), and carrying out bacteria breaking treatment by using an ultrasonic cell disruption instrument; after crushing, the mixture was centrifuged at 10000rpm for 60min using a low-temperature high-speed centrifuge, and the supernatant was collected.
(4) And pouring the obtained crude protein supernatant into an affinity chromatographic column containing Ni-NTA filler, and eluting by using buffers containing different imidazole concentrations to obtain more uniform protein.
(5) Further purifying by anion exchange chromatography to obtain target protein with charge uniformity.
(6) Further purification was performed by gel filtration chromatography to increase the purity of the target protein and to observe the molecular weight of the protein to determine whether it was a polymer.
Screening JEV NS2B-NS3pro inhibitors;
Bz-NKRR-AMC polypeptide compound (available from Shanghai Jier Biochemical Co., ltd.) with purity of 95% was used as a substrate; kinetic curves were determined by fluorescence resonance energy transfer. The instrument for measuring the fluorescence intensity isPro full-wavelength multifunctional microplate detector, corresponding incident and emission wavelengths are 355nm and 460nm, respectively.
The protein buffer fraction was 20mM Tris,30% glycerol, 0.5mM ChAPS,pH 9.0. JEV NS2B-NS3pro (final concentration 2. Mu.M) was prepared with buffer, 89. Mu.L of protein solution was added with 1. Mu.L of compound dissolved in 95% DMSO (final concentration 20. Mu.M), left to stand at 37℃for 5min, 10. Mu.L of Bz-NKRR-AMC (final concentration 20. Mu.M) was added, and shaking at 654rpm was carried out for 10s, and fluorescence readings were recorded every 30 s. The negative control test uses 95% dmso instead of the compound sample, and the other experimental conditions are the same.
The enzymatic kinetics was measured using an microplate reader and the slope of the first 300s was analyzed as the initial rate of the enzymatic reaction. Set V 0 At the initial speed without inhibitor, V i Is the initial speed of adding inhibitor. Calculating each compound according to the initial velocityInhibition Ir (Inhibition Rate, ir) of the substance against JEV NS2B-NS3pro (1-V i /V 0 ) Residual Activity Ra (Residual Activity, ra) (V i /V 0 )。
For compounds with an inhibition rate Ir >70%, re-screening and fluorescence quenching experiments are required to eliminate false positive results generated by misoperation. 89. Mu.L of JEV NS2B-NS3pro solution (final concentration 2. Mu.M) was added to the system and reacted with 10. Mu.L of Bz-NKRR-AMC (final concentration 20. Mu.M) for a sufficient period of time to complete the reaction of the substrate, the fluorescence value was recorded as Q1, and 1. Mu.L of the inhibitor was added to the microplate, and the current fluorescence value was recorded as Q2. Then by the formula: qr= (Q1-Q2)/Q2 is 100%, and the fluorescence quenching rate Qr is calculated. If the fluorescence quenching rate is less than 20%, false positives can be eliminated.
3. Tripterine IC 50 Is measured;
assay of Tripterine IC 50 At this time, the protein JEV NS2B-NS3pro required for the experiment was diluted to a final concentration of 2. Mu.M, and the substrate Bz-NlKRR-AMC was prepared to a final concentration of 20. Mu.M. The inhibitor concentrations were then roughly set to 14 based on the results obtained by the preliminary screening, 100. Mu.M, 50. Mu.M, 25. Mu.M, 12.5. Mu.M, 6.25. Mu.M, 3.12. Mu.M, 1.56. Mu.M, 0.78. Mu.M, 0.39. Mu.M, 0.19. Mu.M, 0.05. Mu.M, 0.025. Mu.M, 0.012. Mu.M, and 0.006. Mu.M, respectively. JEV NS2B-NS3pro and tripterine are uniformly mixed and incubated for 10min at 37 ℃, 10 mu L of Bz-NKRR-AMC is added, and a change curve of fluorescence value and time is recorded by an enzyme-labeling instrument. Analyzing JEV NS2B-NS3pro reaction initial rate by using Graphpad prism 8.0 software to obtain a relationship curve of the inverse value of tripterine concentration and the inhibition rate Ir, and finally obtaining the IC 50 Values.
The invention relates to the technical field of pharmacy, in particular to application of tripterine in preparation of anti-Japanese encephalitis virus drugs, and the inhibition rate Ir of tripterine in inhibiting proteolytic cleavage of NS2B-NS3 protease in Japanese encephalitis virus>70%, IC was measured at a substrate concentration of 20. Mu.M 50 The preparation method is 3.42+/-0.75 mu M, has great application potential in preparing small molecule inhibitors of NS2B-NS3 protease in Japanese encephalitis virus, and has hope of becoming a potential medicine for resisting Japanese encephalitis virus infection.
The invention has the advantages and beneficial effects that:
the invention provides an application of tripterine in preparation of anti-Japanese encephalitis virus medicines, which aims at JEV NS2B-NS3 protease targets in Japanese encephalitis viruses, uses the tripterine as an inhibitor of the protease, has good inhibition activity on JEV NS2B-NS3 protease in Japanese encephalitis viruses, and has various carriers and administration modes, and is convenient to use and easy to obtain.
It is to be understood that the above-described embodiments of the present invention are merely illustrative of or explanation of the principles of the present invention and are in no way limiting of the invention. Accordingly, any modification, equivalent replacement, improvement, etc. made without departing from the spirit and scope of the present invention should be included in the scope of the present invention. Furthermore, the appended claims are intended to cover all such changes and modifications that fall within the scope and boundary of the appended claims, or equivalents of such scope and boundary.
Claims (5)
1. The application of the tripterine in preparing the anti-Japanese encephalitis virus medicament is characterized in that the tripterine has a molecular structural formula as follows:
2. the use according to claim 1, characterized in that: the anti-Japanese encephalitis virus medicament comprises the tripterine and one or more pharmaceutically acceptable carriers.
3. The use according to claim 2, characterized in that: the carrier comprises a diluent, an excipient, a filler, a binder, a wetting agent, a disintegrating agent, an absorption enhancer, a surfactant, an adsorption carrier, a lubricant and a synergist.
4. A use according to any one of claims 1-3, characterized in that: the anti-Japanese encephalitis virus drug is selected from granule, powder, syrup, tablet, pill, suppository or their combination.
5. The use according to claim 4, characterized in that: the administration mode of the anti-Japanese encephalitis virus drug comprises oral administration, injection, implantation, external application, spraying, inhalation or a combination thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210585170.5A CN117159558A (en) | 2022-05-27 | 2022-05-27 | Application of tripterine in preparation of Japanese encephalitis virus resistant medicament |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210585170.5A CN117159558A (en) | 2022-05-27 | 2022-05-27 | Application of tripterine in preparation of Japanese encephalitis virus resistant medicament |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117159558A true CN117159558A (en) | 2023-12-05 |
Family
ID=88932287
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210585170.5A Pending CN117159558A (en) | 2022-05-27 | 2022-05-27 | Application of tripterine in preparation of Japanese encephalitis virus resistant medicament |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117159558A (en) |
-
2022
- 2022-05-27 CN CN202210585170.5A patent/CN117159558A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gupta et al. | Dengue in india | |
| CN116236580B (en) | Application of old drugs such as Auranofin and their combination in combating single positive strand RNA viruses | |
| CN113244211B (en) | Application of baicalein and baicalin in preparing 3CL protease inhibitor of coronavirus SARS-CoV-2 | |
| CN113197895B (en) | A kind of medicinal application of ketoamide compound | |
| CN115466225B (en) | An amide compound and its preparation method, pharmaceutical composition and use | |
| CN113332363B (en) | Application of tea extract and its composition in anti-coronavirus | |
| Pitakbut et al. | Activity of THC, CBD, and CBN on human ACE2 and SARS-CoV1/2 main protease to understand antiviral defense mechanism | |
| Kabi et al. | Overview of Hydroxychloroquine and Remdesivir on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) | |
| CN117159558A (en) | Application of tripterine in preparation of Japanese encephalitis virus resistant medicament | |
| WO2018192083A1 (en) | Zika virus protease inhibitors and methods of use thereof | |
| CN117180253A (en) | Application of chlorcyanosamide in the preparation of anti-Japanese encephalitis virus drugs | |
| Zhao et al. | Yellow fever: a Re-emerging threat | |
| CN113876794A (en) | Potential application of punicalagin in resisting Japanese encephalitis virus infection | |
| CN117159517A (en) | Application of hypericin in preparation of anti-St.Louis encephalitis virus infection medicine | |
| Morchang et al. | Heteropsine inhibits dengue virus infection, suppresses cytokine/chemokine gene expressions, and attenuates nuclear translocation of nuclear factor-kappaB in liver cell lines | |
| CN113827599A (en) | Potential application of demethylzelaronal in resisting dengue virus infection | |
| CN113116872B (en) | Application of Pterostilbene in Anti-Influenza A Virus Drugs | |
| CN114053394B (en) | Application of novel compound in preparation of medicines for preventing and/or treating coronavirus infection | |
| CN115197183B (en) | Sulfur-containing dibenzofuran type compound and preparation method and application thereof | |
| CN100502865C (en) | Application of a compound in the preparation of anti-AIDS drugs | |
| Beringer | The inhibition of SARS-CoV-2 Papain-like protease by tanshinones | |
| Shabani et al. | Investigating the Mechanism of Action of SARS-CoV-2 Virus for Drug Designing: A Review | |
| Rajan A et al. | Phytomolecules having flavone and napthofuran nucleus exhibited better binding G-score against protease and SPIKE protein of novel corona virus COVID-19. | |
| Yousaf et al. | A Comprehensive Review of Dengue Fever: Epidemiological Trends, Diagnostic Approaches, Novel Therapeutic Strategies, and Challenges in Vaccine Advancement over the Past Five Years in the Context of Globalization and Climatic Change: Dengue Fever: Novel Therapeutic Strategies and Vaccine Advancement | |
| CN101108178A (en) | Application of a cyclophilin A inhibitor in the preparation of anti-AIDS drugs |
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 |