CN111317737B - ACCase inhibitor CP640184 as medicine for treating and/or preventing dengue virus infection and pharmaceutical application thereof - Google Patents
ACCase inhibitor CP640184 as medicine for treating and/or preventing dengue virus infection and pharmaceutical application thereof Download PDFInfo
- Publication number
- CN111317737B CN111317737B CN202010112830.9A CN202010112830A CN111317737B CN 111317737 B CN111317737 B CN 111317737B CN 202010112830 A CN202010112830 A CN 202010112830A CN 111317737 B CN111317737 B CN 111317737B
- Authority
- CN
- China
- Prior art keywords
- dengue virus
- protein
- treating
- medicine
- virus infection
- 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.)
- Active
Links
Images
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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
-
- 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
Abstract
The invention relates to a medicament for treating and/or preventing dengue virus infection and pharmaceutical application thereof, and particularly discloses application of a compound shown as a formula I or a pharmaceutically acceptable salt thereof in preparing a medicament for treating and/or preventing dengue virus infection
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an ACCase inhibitor CP640184 as a medicine for treating and/or preventing dengue virus infection and pharmaceutical application thereof.
Background
Dengue virus (DENV) genus Flaviviridae, flaviviridae (Flaviviridae), is a most widespread insect-borne virus in the world today, and dengue is mainly caused by transmission of biting aedes aegypti and aedes albopictus, among which dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) is more severe.
The virus has four serotypes (types 1-4), is an acute infectious disease transmitted by mosquito vectors, and is mainly prevalent in tropical and subtropical regions. Dengue epidemics were developed in succession around the world since the first discovery of dengue in 1779. According to the WHO estimates that about 2/5 of the world's population is currently threatened by dengue fever, billions of people are infected with the virus each year. In China, except for Taiwan regions, the epidemic situation is mainly concentrated in Guangdong and is characterized by outbreak and importation epidemic, and known 4 serotype dengue viruses are discovered in China and tend to spread and increase.
At present, the dengue virus infection mechanism is still unclear, and because effective cross protection is lacked among serotypes and an antibody-dependent enhancement effect exists, so far, safe and effective vaccines are not available, and no effective treatment medicine exists clinically. Although many active molecules against the main proteins of dengue virus are discovered, no drug or vaccine against dengue virus is currently on the market for various reasons (such as toxic and side effects), so that the discovery of the antiviral active molecules against dengue virus has important biological research and practical significance, and provides support for developing effective drugs against dengue virus.
The compound CP640186 related by the invention is an isoenzyme non-selective acetyl-CoA carboxylase (ACCase) inhibitor. The application of CP640186 in preparing the medicine for treating and/or preventing dengue virus infection is disclosed for the first time, and as the framework type belongs to a brand-new framework type and has good effect on dengue virus inhibitory activity, the possibility that other compounds give any revelation does not exist, the CP640186 has outstanding substantive characteristics, and meanwhile, the CP640186 has obvious progress in treating and preventing dengue virus infection and is very likely to be developed into a novel medicine for resisting dengue virus infection.
Disclosure of Invention
The invention aims to provide CP640186, namely application of a compound shown in formula I or a pharmaceutically acceptable salt thereof in preparation of a medicine for treating and/or preventing dengue virus infection, wherein the inhibition rate of CP640186 on dengue virus type 2 at a concentration of 5.0 mu M is 100%. The survival rate of CP640186 on BHK-21 cells under 5.0 μ M condition was 94.37%. CP640186 can effectively inhibit the proliferation of dengue virus, has low cytotoxicity alone, can be further developed into a drug for treating dengue virus infection, and has wide application prospect.
The structure of the compound CP640186 is shown as formula I:
the compound CP640186 related by the invention is an isoenzyme non-selective acetyl-CoA carboxylase (ACCase) inhibitor. The application of CP640186 in preparing the medicine for treating and/or preventing dengue virus infection is disclosed for the first time, the CP640186 has good effect on dengue virus inhibitory activity, the possibility that other compounds give any revelation does not exist, the CP640186 has prominent substantive characteristics, and meanwhile, the CP640186 has obvious progress in treating and preventing dengue virus infection and is very likely to be developed into a novel medicine for resisting dengue virus infection.
One aspect of the present invention provides the use of a compound of formula I or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment and/or prevention of flavivirus infection
In another aspect, the invention provides the use of a compound of formula I or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment and/or prevention of dengue virus infection
In the technical scheme of the invention, the dengue virus is dengue virus 1-4.
In the technical scheme of the invention, the dengue virus is dengue virus type 2.
In still another aspect, the present invention provides a use of a compound represented by formula I or a pharmaceutically acceptable salt thereof in the preparation of a medicament for inhibiting mRNA of E protein in dengue virus
In a further aspect, the invention provides the use of a compound of formula I or a pharmaceutically acceptable salt thereof in the preparation of a medicament for inhibiting protein expression of the E protein in dengue virus
In a further aspect of the present invention, there is provided a pharmaceutical composition for the treatment and/or prevention of dengue virus infection, which comprises as an active ingredient a compound of formula I or a pharmaceutically acceptable salt thereof
In the technical scheme of the invention, the pharmaceutical composition is an injection preparation, an oral preparation or an external preparation.
In the technical scheme of the invention, the pharmaceutical composition is a tablet, a capsule, powder, a pill, a granule, an injection or an emulsion.
Drawings
FIG. 1 shows the inhibitory effect of CP640186 on BHK-21 intracellular viral RNA after DENV2 infection.
FIG. 2 shows the inhibitory effect of CP640186 on the synthesis of viral proteins in BHK-21 cells after DENV2 infection.
FIG. 3 is a graph of the inhibitory effect of CP640186 on intracellular viral replication of BHK-21 following DENV2 infection.
Detailed Description
The technical solutions of the present invention are further described below with reference to specific embodiments and drawings, but it should be understood that the scope of the present invention is not limited by the specific embodiments.
Example 1 toxicity test of CP640186 against BHK-21 cells:
BHK-21 cells (baby hamster kidney cells) are susceptible cells to DENV 2. BHK-21 cells in the experiment were owned by the same laboratory; MTT was purchased from bio-technical institute in bi yun tian; fetal bovine serum was purchased from GIBICO, USA; cell culture plates were purchased from corning, usa; RPMI 1640 medium was purchased from GIBICO, USA.
The experimental procedure was as follows:
1. inoculation of BHK-21 cells: preparing single cell suspension by using RPMI 1640 culture medium containing 10% (V/V) fetal bovine serum, and inoculating 10000 cells per hole into a 96-hole cell culture plate, wherein the inoculation volume per hole is 100 mu l;
2. culturing BHK-21 cells: at 37 ℃ 5% (V/V) CO 2 Culturing for 24 hours under the culture condition;
3. CP640186 was added: the medium in each well was aspirated, 100. Mu.l of CP640186 diluted to the corresponding concentration with 10% (V/V) fetal bovine serum in RPMI 1640 medium was added to each well, and 100. Mu.l of drug-free 10% (V/V) fetal bovine serum in RPMI 1640 medium was added to the control wells;
4. color generation: after 48 hours of incubation, 10. Mu.l of 5mg/ml MTT solution was added to each well at 37 ℃ with 5% (V/V) CO 2 Continuously culturing for 4 hours under the culture condition, then adding DMSO, and observing under a common optical microscope until the Formazan is completely dissolved;
5. measurement and calculation: the absorbance at 570nm was measured, and the viability of the cells at different concentrations of CP640186 was determined by comparing the absorbance of the cells at that concentration to the absorbance of the upper control well, multiplied by 100%, and the results are shown in Table 1.
TABLE 1 toxicity test of CP640186 at various concentrations on BHK-21 cells
The experimental results prove that CP640186 with different concentrations has no influence on the survival rate of BHK-21, and CP640186 is low in toxicity.
Example 2 inhibition experiment of CP640186 on DENV 2:
BHK-21 was used as a cell for culturing the virus DENV2, 10TCID 50 The experimental procedure was as follows:
BHK-21 is inoculated into a cell culture plate, after 24 hours, the cells grow to a monolayer, the area of the cell covering the bottom of a hole is about 80% -90%, the culture medium is sucked out, PBS is washed for 2 times, 100 mu l of virus sample is inoculated, and the virus sample is adsorbed for 1 hour at 37 ℃. After adsorption, the virus fluid in each well was discarded. Adding CP640186 diluted in RPMI 1640 medium containing 2% (V/V) fetal calf serum at 37 deg.C and 5% (V/V) CO 2 Culturing under the culture condition. After 96 hours, CCK was added after the cells had developed significant cytopathic effects8 μ l of a mixture of 5% (V/V) CO at 37 ℃ in the absence of light 2 Culturing for 3 hr under the culture condition, measuring absorbance at 450nm, and determining the survival rate of cells at different concentrations of CP640186 as 1- (experimental group-control group) × 100/(dengue group-control group), wherein the control group is normal cell group without any addition; dengue group: the control group was treated with virus and the group without drug; experimental groups: the group of CP-640186 is added on the basis of the dengue group. The results are shown in Table 2.
TABLE 2 Effect of different concentrations of CP640186 on DENV 2-infected BHK-21
The experimental results are as follows: the experimental result shows that CP640186 has strong protective effect on BHK-21 cell death caused by DENV2 infection under the concentration of 5 mu M, and the inhibition effect reaches 100%. At this concentration, BHK-21 cells survived approximately 94.37%.
Example 3 mRNA inhibition assay of CP640186 against the E protein, a key protein of DENV2
1. Collecting total RNA of cells: adding 1ml of Trizol reagent (ambion) into each well of a 6-well cell culture plate, standing at room temperature for 5 minutes, and then sucking supernatant into a 1.5ml Eppendorf tube; adding 0.2ml of chloroform into each tube, shaking, incubating for 15 minutes at room temperature, centrifuging for 15 minutes at 4 ℃ at 12000rpm, and absorbing the upper-layer liquid phase to transfer into another 1.5ml Eppendorf tube; adding 0.5ml of isopropanol, shaking, incubating for 10 minutes at room temperature, and centrifuging for 10 minutes at 12000rpm at 4 ℃; removing supernatant by suction, adding 1ml of 75% (V/V) ethanol, washing precipitate, centrifuging at 4 ℃ and 12000rpm for 10 minutes, and removing supernatant by suction; drying at room temperature to make it transparent; adding DEPC (diethyldithiocarbamate) treatment double distilled water 20 mu l to dissolve RNA, and storing at-80 ℃ for later use; and detecting the ratio of the absorbance 260 to the absorbance 280 by using an ultraviolet spectrophotometer, and calculating the RNA concentration.
2. Reverse transcription of RNA into cDNA: reaction system: RNA 1mg,5 XPrimeScript RT Master Mix (TAKARA) 4. Mu.l, DEPC treated triple distilled water to a total volume of 20. Mu.l. Carefully mix and then mix at 37 ℃ for 15min and 85 ℃ for 5 seconds.
3. Real-time fluorescent quantitative PCR detection of each sampleRNA level of the viral envelope protein and non-structural protein 1: reaction system (10. Mu.l): mu.l of cDNA template was added to the reaction mixture,
qPCR Master Mix (Promega) 5. Mu.l, forward and reverse primers 0.4. Mu.l, DEPC treated triple distilled water 3.2. Mu.l. After mixing, the mixture was pre-denatured at 95 ℃ for 10 minutes, at 95 ℃ for 15 seconds and at 60 ℃ for 1 minute (40 cycles).
TABLE 3 Forward and reverse primers for each target RNA
4. And (3) calculating: and calculating the RNA level of each sample relative to the control group by using a 2-delta C T-T method according to the CT value of each sample.
The experimental results are as follows: referring to figure 1, mRNA levels of DENV2 key protein E protein were significantly reduced and concentration dependent after cp640186 treatment. At concentrations of 2.5 and 5 μ M, the mRNA level of the E protein was significantly reduced. Showing its ability to inhibit the replication and amplification of dengue virus.
Example 4 protein expression inhibition assay of CP640186 against DENV2 Virus Key protein E protein
1. Collecting total cellular protein: after BHK-21 cells were treated with drug and dengue virus (DENV 2), protein was extracted 48 h: the cells were washed with cold PBS, 100. Mu.l of RIPA lysate (Kayaki organism) plus phosphatase inhibitor (Kayaki organism) plus protease inhibitor (Kayaki organism)) was added to each well of 6-well plate, collected by scraping with a spatula in 1.5ml Eppendorf tubes, centrifuged at 12000rcf at 4 ℃ for 15min, and the supernatant was transferred to a new Eppendorf tube.
2. Detecting the protein concentration of the sample: diluting the protein standard substance with double distilled water to gradient concentration of 0,0.0008,0.0016,0.0032,0.004,0.006, 0.008mg/ml; adding 2.5 mul of each of the protein standard substance and the protein sample into a 24-pore plate, adding 1.5ml of 1 XG 250 working solution into each pore, enabling the final volume of each pore to be 2.5ml, shaking for 3 minutes at room temperature, and measuring the absorption of 570nm in each pore by using an enzyme-labeling instrument; the protein concentration in the sample was calculated from the standard curve. Data were processed and samples were added to corresponding volumes of RIPA lysate and loading buffer to make consistent protein concentrations for each sample. Denaturing at 100 deg.c for 5min and storing at-20 deg.c for further use.
3. The western blotting was performed to detect the expression difference of dengue virus protein after the treatment of gradient concentration CP 640186: 10% SDS Polyacrylamide gel preparation: adding various reagents in sequence, preparing 10% separation gel, rapidly filling in glass gap, flowing out the time required for filling concentration gel (about 0.8cm of the lower edge below the comb), rapidly covering a layer of anhydrous ethanol on the separation gel, pouring off the anhydrous ethanol layer after polymerization of the separation gel, sucking with filter paper, continuously filling the concentration gel, and inserting the comb. Electrophoresis: and switching on a power supply, performing electrophoresis at a constant voltage of 80V initially, changing the voltage to 120V after the front edge of the dye enters the separation gel, and determining the electrophoresis time according to the separation degree of the pre-dyed protein Marker and the molecular weight of the target protein, wherein the electrophoresis time generally runs for about 75 min.
4. Film transfer: the gel was removed from the glass plate, sheared and soaked in methanol for 1min, followed by a 5min soak in transfer buffer (1 × tris/glycine buffer, biorad). Soaking the gel, the filter paper and the PVDF membrane in the transfer liquid, and installing a membrane transfer device in the following sequence: the negative electrode, the cotton pad, the filter paper, the gel, the PVDF film, the filter paper, the cotton pad and the positive electrode are stacked one by one and accurately aligned. And (3) placing the membrane rotating device in a membrane rotating box, confirming that the electrodes are correct, adding the membrane rotating liquid to cover the whole membrane rotating device, covering the membrane rotating box and the upper part of the membrane rotating box with ice blocks, switching on a power supply, rotating the membrane at a constant voltage of 100V for about 70min, and taking out the PVDF membrane after the operation is finished.
5. Protein blocking: and (3) placing the PVDF membrane in a sealing solution, and soaking for 1h in a shaking table at room temperature to seal the nonspecific antigen. After blocking, the TBS/TT was shaken 3 times at room temperature for 5min each time followed by incubation of one antibody.
6. Primary antibody hybridization: the PVDF membrane protein face up was placed in a small box, and 5% (w/v) skim milk buffer in TBS/T formulation containing a Dengue virus Envelope protein (GeneTex) and nonstructural protein 1 (Dengue virus NS3glycoprotein antibody, abcam) primary antibody was added and shaken overnight at 4 ℃. The membrane was washed with PBST for 5min six times at room temperature by shaking.
7. And (3) hybridization of a second antibody: the PVDF membrane protein face up was placed in a small box, and 5% (w/v) skim milk buffer in TBS/T formulation containing secondary antibody (rabbit antibody or mouse antibody, proteitech) was added and shaken for 1 hour at room temperature. The membrane was washed with PBST for 5min six times at room temperature by shaking.
8. And (3) chemiluminescence development: and uniformly adding ECL developing solution A/B (CST) according to a proportion, soaking the PVDF film in a luminescent solution, and reacting for 2min. Taking out the PVDF film, placing in a cassette, exposing in a dark room, placing an X-ray negative film, exposing, taking out for development, airing the film, recording and storing.
The experimental results are as follows: referring to fig. 2, after cp640186 treatment, DENV2 key protein E protein expression levels were significantly reduced and concentration-dependent. At concentrations of 5 and 10 μ M, the expression level of E protein was significantly reduced, consistent with the results at the gene level. It is shown that it indeed has the effect of inhibiting the expression of key proteins of dengue virus.
Example 5 Confocal assay of CP640186 against DENV2 Virus
1. BHK-21 cells were inoculated into a Confocal dish, and 24 hours later, the cells grew to a monolayer (the area of the cell covering the bottom of the well was about 70-80%), the medium in each well was discarded, washed 2 times with PBS, and 1ml of a virus sample prepared in serum-free RPMI 1640 medium was inoculated and adsorbed at 37 ℃ for 1 hour.
2. After completion of the adsorption, the virus supernatant from each well was discarded, and the unadsorbed virus was washed away with PBS. 5 μ M CP640186 diluted in RPMI 1640 medium containing 2% (V/V) fetal bovine serum was added at 37 deg.C and 5% (V/V) CO 2 Was cultured in an incubator for 48 hours.
3. After discarding the medium and fixing the cells in 4% (wt/vol) paraformaldehyde and treating with 0.1% (vol/vol) Triton X-100, the cells were stained with primary antibody (virus Envelope protein (GeneTex)) (2. Mu.g/ml) at 4 ℃ overnight. Then, after washing 3 times with PBS, fluorescein isothiocyanate or tetramethylrhodamine isothiocyanate conjugated secondary antibody (Sigma, MO, USA) was added and incubated at room temperature for 2 hours. After 3 washes with PBS, the images were processed by confocal microscopy (Zeiss, jena, germany).
The experimental results are as follows: referring to FIG. 3, the Confocal experiment of the virus determined the amount of virus produced in the host cells following virus infection. The results show that the production of virus in host cells is significantly reduced after treating DENV2 virus infected BHK-21 cells with CP 640186.
The above description is only a specific embodiment of the present invention, and not all embodiments, and any equivalent modifications of the technical solutions of the present invention, which are made by those skilled in the art through reading the present specification, are covered by the claims of the present invention.
SEQUENCE LISTING
<110> southern medical university
<120> ACCase inhibitor CP640184 as medicament for treating and/or preventing dengue virus infection and pharmaceutical use thereof
<130> CP120010036C
<160> 4
<170> PatentIn version 3.3
<210> 1
<211> 20
<212> DNA
<213> Artificial sequence
<400> 1
<210> 2
<211> 20
<212> DNA
<213> Artificial sequence
<400> 2
<210> 3
<211> 23
<212> DNA
<213> Artificial sequence
<400> 3
tgacctcaac tacatggtct aca 23
<210> 4
<211> 19
<212> DNA
<213> Artificial sequence
<400> 4
cttcccattc tcggccttg 19
Claims (5)
1. Use of compound shown as formula I or pharmaceutically acceptable salt thereof in preparation of medicine for treating and/or preventing dengue virus infection
The dengue virus is dengue virus type 2.
2. Application of compound shown as formula I or pharmaceutically acceptable salt thereof in preparing medicine for inhibiting mRNA of E protein in dengue virus
3. Use of compound shown as formula I or pharmaceutically acceptable salt thereof in preparation of medicine for inhibiting protein expression of E protein in dengue virus
4. Use according to any one of claims 1 to 3, wherein the medicament is an injectable, oral or topical formulation.
5. Use according to any one of claims 1 to 3, characterized in that the medicament is a tablet, capsule, powder, pill, granule, injection or emulsion.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010112830.9A CN111317737B (en) | 2020-02-24 | 2020-02-24 | ACCase inhibitor CP640184 as medicine for treating and/or preventing dengue virus infection and pharmaceutical application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010112830.9A CN111317737B (en) | 2020-02-24 | 2020-02-24 | ACCase inhibitor CP640184 as medicine for treating and/or preventing dengue virus infection and pharmaceutical application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111317737A CN111317737A (en) | 2020-06-23 |
| CN111317737B true CN111317737B (en) | 2023-02-17 |
Family
ID=71168959
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010112830.9A Active CN111317737B (en) | 2020-02-24 | 2020-02-24 | ACCase inhibitor CP640184 as medicine for treating and/or preventing dengue virus infection and pharmaceutical application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111317737B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101795701A (en) * | 2007-05-14 | 2010-08-04 | 纽尔雅制药公司 | Inhibitors of acetyl-COA carboxylase for treatment of neuronal hypometabolism |
| CN101820757A (en) * | 2007-06-01 | 2010-09-01 | 普林斯顿大学托管委员会 | By regulating host cell metabolic pathways treatment virus infections |
| CN109602746A (en) * | 2019-02-12 | 2019-04-12 | 南方医科大学 | The drug and its pharmaceutical applications for treating dengue virus infection |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012139028A2 (en) * | 2011-04-06 | 2012-10-11 | The Trustees Of Princeton University | Anti-viral combination therapy |
-
2020
- 2020-02-24 CN CN202010112830.9A patent/CN111317737B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101795701A (en) * | 2007-05-14 | 2010-08-04 | 纽尔雅制药公司 | Inhibitors of acetyl-COA carboxylase for treatment of neuronal hypometabolism |
| CN101820757A (en) * | 2007-06-01 | 2010-09-01 | 普林斯顿大学托管委员会 | By regulating host cell metabolic pathways treatment virus infections |
| CN109602746A (en) * | 2019-02-12 | 2019-04-12 | 南方医科大学 | The drug and its pharmaceutical applications for treating dengue virus infection |
Non-Patent Citations (2)
| Title |
|---|
| Fatty Acids Regulate Porcine Reproductive and Respiratory Syndrome Virus Infection via the AMPK-ACC1 Signaling Pathway;Siwen Long等;《Viruses》;20191210;第11卷(第1145期);第2页第1段、第8页最后一段、第10页第2段 * |
| Liver-specific mono-unsaturated fatty acid synthase-1 inhibitor for anti-hepatitis C treatment;Yasunori Nio等;《Antiviral Research》;20160705;第132卷;第264页左栏第2段、第265页左栏第3段 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111317737A (en) | 2020-06-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Rapp et al. | Differential effects of inhibitors on the steps leading to the formation of SV40 tumor and virus antigens | |
| CN107441094B (en) | Nilotinib as medicine for treating dengue virus infection and pharmaceutical application thereof | |
| Burivong et al. | Markedly reduced severity of Dengue virus infection in mosquito cell cultures persistently infected with Aedes albopictus densovirus (AalDNV) | |
| CN111402968B (en) | New application of kaempferol in COVID-19 virus based on molecular simulation | |
| Perry et al. | Murine norovirus-1 entry into permissive macrophages and dendritic cells is pH-independent | |
| Newman et al. | Antiviral effects of oleandrin | |
| CN113813269B (en) | Application of Perifosine in preparation of anti-Hantaan virus medicine | |
| CN111317737B (en) | ACCase inhibitor CP640184 as medicine for treating and/or preventing dengue virus infection and pharmaceutical application thereof | |
| CN109602749B (en) | Britinib as medicine for treating dengue virus infection and pharmaceutical application thereof | |
| CN111973600B (en) | Application of mycophenolic acid or derivative thereof in preparation of canine distemper virus inhibitor | |
| CN109602746B (en) | Medicine for treating dengue virus infection and pharmaceutical application thereof | |
| CN106983736B (en) | Drug and its pharmaceutical applications of the Tatanan A as treatment dengue virus infection | |
| CN110755436A (en) | Medicine for preventing Zika virus infection and application of lycorine in preparation of medicine for preventing Zika virus infection | |
| CN111346079B (en) | Bacterial DNA gyrase inhibitor BRD7716 as medicament for treating and/or preventing dengue virus infection and pharmaceutical application thereof | |
| Zhu et al. | Grass Carp Reovirus triggers autophagy enhancing virus replication via the Akt/mTOR pathway | |
| Dolzhikova et al. | Ebola virus (Filoviridae: Ebolavirus: Zaire ebolavirus): fatal adaptation mutations | |
| CN106860437B (en) | Drug and its pharmaceutical applications of the diasarone I as treatment dengue virus infection | |
| CN101781651B (en) | Target small-interfering RNA sequence for restraining replication of I-type dengue virus | |
| CN105012935A (en) | Application of IFITM3 protein loaded exosome in preparation of anti-dengue virus interferon antagonism strain infection drugs | |
| WO2022228581A1 (en) | Application of 1,5-dehydrated sorbitol in preparation of drugs for treating and preventing diseases caused by sars-cov-2 virus | |
| CN113750083B (en) | Application of metformin in preparation of medicine for treating hand-foot-and-mouth disease | |
| CN113546076B (en) | Application of verteporfin in preparing medicine for resisting novel coronavirus SARS-CoV-2 | |
| CN110433148A (en) | Application of the Tenovin-1 in preparation treatment and/or prevention dengue virus infection drug | |
| KR102091372B1 (en) | Inactivated Enterovirus 71 Vaccine and Uses Thereof | |
| BR102021002958A2 (en) | USE OF BAZEDOXYPHENE IN ANTIVIRAL MEDICINES |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |