CN106563127A - Application of statin compounds in blocking of Ebola virus invasion infection - Google Patents
Application of statin compounds in blocking of Ebola virus invasion infection Download PDFInfo
- Publication number
- CN106563127A CN106563127A CN201610852206.6A CN201610852206A CN106563127A CN 106563127 A CN106563127 A CN 106563127A CN 201610852206 A CN201610852206 A CN 201610852206A CN 106563127 A CN106563127 A CN 106563127A
- Authority
- CN
- China
- Prior art keywords
- ebola virus
- statin compound
- application
- blocking
- 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.)
- Pending
Links
Classifications
-
- 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
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
Landscapes
- 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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides an application of statin compounds in blocking of Ebola virus invasion infection, wherein the statin compounds include but are not limited to fluvastatin and simvastatin. The statin compounds can effectively block the invasion stage of Ebola virus and are possible to be further developed into Ebola virus entering inhibitors, so a theoretical basis is provided for development of an antiviral combined drug with the statin compounds as main components, and a science technical support is provided for prevention and control of virus newly emerging infectious diseases.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of statin compound is in blocking Ebola virus invasion sense
Application in dye, wherein statin compound include but is not limited to the statin compounds such as Fluvastatin and Simvastatin.
Background technology
Ebola hemorrhagic fever is that a kind of acute hemorrhagic caused by Ebola virus (Ebola virus, EBOV) is infected
Disease.Mainly infected by the blood of contact patient or infection animal, body fluid, secretion and excreta etc., clinical main performance
For projection heating, bleeding and multiple organ damage.The Ebola virus epidemic situation of outburst in 2014 has swept across West Africa various places, high cause
Dead rate causes global fear.
Ebola virus (EBOV) belongs to filamentous virus section, thread in length, is sub-thread minus-stranded rna virus, there is 18959 alkali
Base, there is cyst membrane.Pure virion is made up of a spirality ribonucleocapsid complex, the molecule of linear rna containing minus strand and 4 virions
Structural proteins.The viral genome codes of Ebola are containing seven structural proteins and a non-structural protein.The order of gene is：3’
End-NP-VP35-VP40-GP-VP30-VP24-L-5 ' holds, and each of which protein product is by a kind of single
Coded by mRNA.So far, it has been found that 5 kinds of different Ebola viruses.Wherein 4 kinds are found in first Africa, to the mankind and inhuman
Class primate has pathogenecity.Five kinds of viruses are respectively the Sudan Ebola virus (SEBOV is found in 1976), prick
Ilyushin Ebola virus (ZEBOV is found in 1976), Cote d'lvoire Ebola virus (CIEBOV is found in 1994) and
Ben Dibujiao Ebola viruses (BEBOV is found in 2007).(REBOV sends out for 5th kind of virus, i.e. Reston Ebola virus
Now in 1989), Philippine is only found in, seem only to cause disease in non-human, primate and hog so far.It is different
Strain there are different toxicity, wherein Zaire Ebola virus (ZEBOV) fatal rate highest.
Due to there is no the effective medicine through system research to be used for the treatment of EVD patient, current treatment method is with product
To the ill and based on supportive treatment of pole, mainly includes：Water, electrolyte balance are maintained, body fluid and electrolyte is supplemented；Prevention and control
Bleeding, maintains blood oxygen and blood pressure balance, and scabies secondary infection is controlled in time；Treatment renal failure and bleeding, dispersivity Ink vessel transfusing coagulates
Blood (DIC:Disseminate intravascular coagula tion) etc. complication.Additionally, due to Ebola rehabilitation clients's
Serum is invalid without remarkable effect, common antiviral method, such as interferon, Ribavirin in treatment disease[2].EBOV's
Before vaccine research and development start from 20 years, panimmunity strategy and animal pattern are had at present, but there is no a kind of vaccine to ratify by FDA.
It, uniquely in the glycoprotein of virus surface, is also topmost immune targets that EBOV glycoprotein is.EBOV vaccines are passed according to antigen
Sending mode to be broadly divided into three classes is included based on the vaccine of non-replicating viral vector, the vaccine and base based on replicating viral vector
In the vaccine of virus protein antigens, wherein being developed jointly by GlaxoSmithKline PLC company and American National allergy and Infectious Disease Research Institute
ChAd3-ZEBOV and by the VSV-EBOV mixed type vaccines that Canadian PHS is developed be it is most potential, at present
Into clinical investigation phase, but still need to more researchs and have shown that its validity.
Compared with vaccine, small-molecule drug production is rapid, production capacity is stable in properties greatly, is resistant to normal temperature storage and transport,
Can be administered by the oral way of Noninvasive, without the need for relying on special installation, for by body fluid, contact transmission angstrom
Rich drawing virus infection has preferable Therapeutic safety, and production of vaccine cycle length, price can be overcome high, active unstable and anti-
Former multifarious shortcoming.In addition, based on marketed drug, screening can effectively block the small molecule that EBV is entered and replicated
Compound, the research and development probability of new drug can not only be made significantly to be lifted and also can effectively shorten the production cycle and reduce pharmacy into
This, the urgent preventing and treating for the infection of national Ebola virus provides support
The content of the invention
The invention provides a kind of application of statin compound in blocking Ebola virus invasion infection.
The purpose of the present invention is achieved through the following technical solutions：
Application of the statin compound in blocking Ebola virus invasion infection.
Preferably, the structural formula of the statin compound is as shown in figure 3, wherein A:One with HMG-CoA structure classes
β, δ-dihydroxy-acid structure；
B:Hydrophobic cyclic structure；
C:The coupling part of A and B, can be ethyl, ethene etc..
Preferably, described statin compound includes Fluvastatin, Simvastatin.
Preferably, described statin compound is Fluvastatin, and the Fluvastatin structural formula is as follows：
Preferably, the statin compound is Simvastatin, and the Simvastatin structural formula is as follows,
Preferably, the Ebola virus includes Zaire's type, the Sudan's type, Christopher Eccleston type, Cote d'lvoire's type and Uganda
Ben Dibujiao types.
Preferably, the Ebola virus is Zaire's type.
Preferably, application of the statin compound in anti-ebola disease cytotoxic drug.
Beneficial effects of the present invention are embodied in：A kind of application of inhibin in blocking Ebola virus invasion infection.Institute
The inhibin stated is statin compound.The present invention is entered for the Ebola virus developed with statin compound as main component
Inhibitor is provided fundamental basis, and to treat and prevent Ebola virus infection a kind of method is provided, and to viral emerging infectious disease
Prevention and control provide science and technology support.
Description of the drawings
Fig. 1 is the effect assessment that Fluvastatin blocks Ebola virus invasion infection.
Fig. 2 is the effect assessment that Simvastatin blocks Ebola virus invasion infection.
Fig. 3 is the structural representation of statin compound.
Specific embodiment
Technical scheme and its performance study are specifically described with reference to embodiments
Embodiment 1：EBOV GP-HIV screening system principles
Into the first step that host cell is virus infection, suppressing the entrance of virus can effectively block disease to Ebola virus
Poison infection.EBOV envelope surface glycoproteins (Glycoprotein.GP) are that mediation Ebola virus is adsorbed and into target cell
Key protein.
We have synthesized coating GP genes (EBV-Zaire GP, the Gene Accesion of Zaire type Ebola virus
No.L11365). by cotransfection EBV-GP and by pNL4-3.Luc.R-E-Cotransfection cells, can obtain EBV-GP for shell bag
The EBV recombinant virus EBV-GP/HIV of the HIV cores wrapped up in.The virion has the characteristics that：1) virus is to host cell
The selective characteristic depending on EBOV-GP；2) due to the env on HIV carriers, nef and vpr gene delections, therefore the virus is only
Host cell and not reproducible can be disposably entered, so the virus is safe；3) fluorescence is carried on the HIV carriers
Plain enzyme reporter gene, therefore infected cell meeting expressing luciferase, by detecting that the activity of luciferase can represent thin
The degree that born of the same parents are infected.
Embodiment 2：Using the antiviral effect of EBOV-GP/HIV pseudovirus system appraisal statin compounds
It is rich to anti-angstrom of statin compound using EBV-Zaire (Gene Accession No.L11365) in the present invention
Poisoning intrusion infection is drawn to carry out pharmacologically active evaluation
It is prepared by recombinant virus：Cotransfection 2ug pcDNA3.1/EBV-GP plasmids and 20ug pNL4-3.Luc.R-E-Plasmid is extremely
293T cells, transfection 48h collects supernatant, supernatant Jing 0.45uM membrane filtrations, containing EBV-GP/HIV viruses in the supernatant
Grain, the recombinant virus can be used to infect.
Infection and detection：Infection the previous day, by every hole 104The density of individual cell is inoculated into Hela cells on 96 orifice plates.
With ethanol (Fluvastatin dissolves in ethanol) or DMSO (Simvastatin is dissolved in DMSO) dissolving positive reference compounds
Or compound to be screened, infect and add within first 15 minutes in cell culture fluid, using ethanol and DMSO as blank, add per hole
The virus liquid (10 of the EBV-GP/HIV-luc of 0.1ul9Rluc/ml) infection cell, after infecting 48 hours, supernatant discarded uses PBS
Wash twice, then add 50ul cell pyrolysis liquids (Promega) to infected cell per well, by 25ul luciferase substrates with
The relative activity of cell fluorescence element enzyme is detected after the mixing of 25ul cell pyrolysis liquids with MD ELIASAs, the power of its activity has reacted disease
The infection level of poison, as a result shows that Fluvastatin and Simvastatin can effectively block the invasion infection of Ebola virus, knot
Fruit sees Fig. 1,2 and table 1.
The effect that the Fluvastatin of table 1 and Simvastatin are infected EBV-GP/HIV
Embodiment 3：Cytotoxicity detection test
Using MTS methods related to medicine is determined in our experimental systems to the cytotoxicity of Hela cells, knot
Fruit shows medicine equal no cytotoxicity under the final concentration of 10uM.
We evaluate many using the Ebola virus reporting system (EBVG/HIV-luc) that can be studied in P-2 laboratories
Micromolecular compound is planted, by the way that experiment is repeated several times, it was found that statin compound has when the invasion of anti-Ebola virus is infected
Obvious inhibition.
Statin compound belongs to a kind of statin compound.Statin compound is to the low-density lipoprotein in blood of human body
In vain (low density lipoprotein, LDL)-cholesterol levels have the effect for reducing.It passes through to suppress methylol penta 2
Acyl coenzyme A (HMG-CoA) reductase, blocks intracellular hydroxyl first valeric acid metabolic pathway, reduces intracellular cholesteryl synthesis, so as to
Feedback sexual stimulus surface of cell membrane LDL receptor quantity and activity increase, increase serum cholesterol removing, level
Reduce.Currently available statin compound include Lovastatin, Simvastatin (simvastatin), Pravastatin, fluorine cuts down
Statin (Fluvastatin), cerivastatin and atropic cut down him.International monopoly WO 00/47196 is related to a kind of for treating
The method of the mammal with hepatitis C, human immunodeficiency virus (HIV), hepatitis B, G types hepatitis or H type hepatitis,
Its by giving patient's at least one inhibin or suppressing on chlorins compound, but WO 00/47196 not do not consider will
The statin compound is applied to prevent and treat the infection of Ebola virus.It is of the invention to be surprisingly found that, statin compound
In can be used for the medicine of anti-Ebola virus infection, wherein statin compound includes but is not limited to Fluvastatin and pungent cuts down him
Spit of fland, can be effectively blocked the invasion stage of Ebola virus, make further progress for Ebola virus entry inhibitor can
Can, it is so as to the antiviral compound medicine for exploitation with statin compound as main component is provided fundamental basis and new to virus
The prevention and control for sending out infectious disease provide science and technology support.
The present invention still has various specific embodiments.All employing equivalents or equivalent transformation and all skills for being formed
Art scheme, all falls within the scope of protection of present invention.
Claims (8)
1. application of the statin compound in blocking Ebola virus invasion infection.
2. application of the statin compound as claimed in claim 1 in blocking Ebola virus invasion infection, its feature exists
In：The structural formula of the statin compound is as shown in figure 3, wherein A:One with β, δ of HMG-CoA structure classes-dihydroxy penta
Sour structure；
B:Hydrophobic cyclic structure；
C:The coupling part of A and B, can be ethyl, ethene etc..
3. application of the statin compound as described in claim 1 in blocking Ebola virus invasion infection, its feature
It is：Described statin compound includes Fluvastatin, Simvastatin.
4. application of the statin compound as claimed in claim 3 in blocking Ebola virus invasion infection, its feature exists
In：Described statin compound is Fluvastatin, and the Fluvastatin structural formula is as follows：
5. application of the statin compound as claimed in claim 3 in blocking Ebola virus invasion infection, its feature exists
In：The statin compound is Simvastatin, and the Simvastatin structural formula is as follows,
6. application of the statin compound as claimed in claim 1 in blocking Ebola virus invasion infection, its feature exists
In：The Ebola virus includes Zaire's type, the Sudan's type, Christopher Eccleston type, Cote d'lvoire's type and Uganda's Ben Dibujiao types.
7. application of the statin compound as claimed in claim 1 in blocking Ebola virus invasion infection, its feature exists
In：The Ebola virus is Zaire's type.
8. application of the statin compound in anti-ebola disease cytotoxic drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610852206.6A CN106563127A (en) | 2016-09-27 | 2016-09-27 | Application of statin compounds in blocking of Ebola virus invasion infection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610852206.6A CN106563127A (en) | 2016-09-27 | 2016-09-27 | Application of statin compounds in blocking of Ebola virus invasion infection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106563127A true CN106563127A (en) | 2017-04-19 |
Family
ID=58532534
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610852206.6A Pending CN106563127A (en) | 2016-09-27 | 2016-09-27 | Application of statin compounds in blocking of Ebola virus invasion infection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106563127A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020142940A1 (en) * | 2000-10-17 | 2002-10-03 | Graham Barney Scott | Method of inhibiting viral infection using HMG-COA reductase inhibitors and isoprenylation inhibitors |
| WO2005023305A2 (en) * | 2003-09-10 | 2005-03-17 | Inpharmatica Limited | Modulating cell activity by using an agent that reduces the level of cholesterol within a cell |
-
2016
- 2016-09-27 CN CN201610852206.6A patent/CN106563127A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020142940A1 (en) * | 2000-10-17 | 2002-10-03 | Graham Barney Scott | Method of inhibiting viral infection using HMG-COA reductase inhibitors and isoprenylation inhibitors |
| WO2005023305A2 (en) * | 2003-09-10 | 2005-03-17 | Inpharmatica Limited | Modulating cell activity by using an agent that reduces the level of cholesterol within a cell |
Non-Patent Citations (3)
| Title |
|---|
| DAVID S.ET AL.: "Treating Ebola patients: a ‘bottom up’ approach using generic statins and angiotensin receptor blockers", 《INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES》 * |
| DAVID S.ET AL.: "Treating the Host Response to Ebola Virus Disease with Generic Statins and Angiotensin Receptor Blockers", 《OPINION/HYPOTHESIS CROSSMARK》 * |
| MORITZ HACKE.ET AL.: "Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol", 《NATURE COMMUNICATION》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10155947B2 (en) | Method for inhibiting Ebola virus via miRNA | |
| CN107106525A (en) | Treatment for suppressing single strand RNA virus duplication | |
| CN105418410B (en) | Emodin derivates and its application in the medicine of AntiHIV1 RT activity 1 is prepared | |
| CN104069096A (en) | Drug for resisting HIV latency and applications thereof | |
| CN106563127A (en) | Application of statin compounds in blocking of Ebola virus invasion infection | |
| CN106562982A (en) | Applications of cardiac glycoside compound in resisting Ebola virus infection | |
| CN102755316A (en) | Application of artemisinin and derivatives thereof in preparation of medicaments for treating hepatitis C viruses | |
| WO1997037661A1 (en) | Preventive and remedy for viral infections | |
| CN106361735A (en) | Application of triparanol to resisting Ebola virus infection | |
| Tan et al. | Understanding human immunodeficiency virus type 1 and hepatitis C virus coinfection | |
| Mao et al. | Roles and mechanisms of exosomal microRNAs in viral infections | |
| CN103054867B (en) | Application of fangchinoline for preparing medicine for treating or preventing HIV | |
| CN109700823A (en) | Application of the Ketek in anti-Ebola virus infects | |
| CN101461805B (en) | Use of anti-hantavirus medicament arbidol | |
| CN103893172B (en) | The application in preparing anti-HIV-1 virus drugs of a kind of antiviral compound | |
| CN104013616B (en) | Amide groups-thiophenes is in the application of preparing in anti-HIV-1 virus drugs | |
| CN105616404A (en) | Application of arbidol in resisting filo virus infection | |
| CN103860552B (en) | The application in preparing anti-HIV-1 virus drugs of a kind of antiviral compound | |
| CN103830232B (en) | A kind of antiviral compound is in the application of preparing in anti-HIV-1 virus drugs | |
| CN102160870A (en) | Application of poly(4-styrenesulfonic acid-co-maleic acid) sodium and medicinal composition thereof | |
| CN107823215A (en) | Application of the scutelloside in the medicine for preparing preventing and treating zika virus infection | |
| CN105031612B (en) | A kind of endoplasmic reticulum albumen of homocysteine induction is preparing the application in treating or preventing EV71 infection medicines | |
| CN104000807B (en) | Phenyl-amides compound is in the application of preparing in anti-HIV-1 virus drugs | |
| CN105477007A (en) | Application of macrolides medicine to prevent inovirus infection | |
| Culmer | Development of Novel Pyridazine Derivatives and Drug Delivery Systems Against Dengue |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170419 |
|
| RJ01 | Rejection of invention patent application after publication |