CN115957222A - Application of Efavirenz in preparation of anti-adenovirus ADV7 drugs - Google Patents
Application of Efavirenz in preparation of anti-adenovirus ADV7 drugs Download PDFInfo
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- CN115957222A CN115957222A CN202211742163.8A CN202211742163A CN115957222A CN 115957222 A CN115957222 A CN 115957222A CN 202211742163 A CN202211742163 A CN 202211742163A CN 115957222 A CN115957222 A CN 115957222A
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- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 229960003804 efavirenz Drugs 0.000 title claims abstract description 34
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 title claims abstract description 34
- 239000003814 drug Substances 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 230000003263 anti-adenoviral effect Effects 0.000 title claims abstract description 7
- 229940079593 drug Drugs 0.000 title abstract description 15
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- 150000001875 compounds Chemical class 0.000 claims abstract description 17
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
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- OAVCWZUKQIEFGG-UHFFFAOYSA-O 2-(5-methyl-2H-tetrazol-1-ium-1-yl)-1,3-thiazole Chemical compound CC1=NN=N[NH+]1C1=NC=CS1 OAVCWZUKQIEFGG-UHFFFAOYSA-O 0.000 description 1
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
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- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- 238000011053 TCID50 method Methods 0.000 description 1
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- 210000000056 organ Anatomy 0.000 description 1
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- 230000003389 potentiating effect Effects 0.000 description 1
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- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
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- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
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- 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 discloses an application of Efavirenz in preparation of an anti-adenovirus ADV7 drug. According to the invention, through an activity research experiment of Efavirenz for resisting ADV7, the compound Efavirenz inhibits a cytopathic effect (CPE) generated by ADV7 on host cells Hela, enhances the cell survival rate, reduces the yield of progeny viruses, and has the potential to be widely applied to the preparation of ADV7 virus resisting medicines.
Description
Technical Field
The invention relates to the technical field of antiviral drugs, and relates to an application of Efavirenz in preparation of an anti-adenovirus ADV7 drug.
Background
Adenoviruses (ADV) are a widely distributed group of DNA viruses. There are 52 known adenovirus types, designated ADVL-ADV 52, which belong to two genera and are about 100 serotypes. About 1/3 of the known serotypes of human adenoviruses are associated with human disease. Adenovirus can invade various tissues and organs such as respiratory tract, eye conjunctiva, gastrointestinal tract and urinary tract, mainly respiratory tract infection, severe cases can cause infantile pneumonia, and can accumulate all systems of the whole body. Adenovirus pneumonia caused by adenovirus infection is one of the most serious types of infantile pneumonia. The adenovirus types associated with respiratory diseases are mainly ADV7, ADV3 and ADV4, wherein ADV7 can cause severe or fatal lower respiratory tract infection of infants and is easy to cause epidemic outbreak. At present, no effective preventive vaccine and therapeutic medicine exist clinically aiming at the infection caused by the virus, and symptomatic treatment is mainly adopted. Therefore, the development of specific and effective anti-ADV 7 drugs is imperative.
Efavirrenz is a potent and selective non-nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) Reverse Transcriptase (RT), the first NNRTI of antiretroviral therapy worldwide. Efavirenz can be used together with other antiretroviral drugs for treating HIV infection, and has the advantages of small dosage, good effect and acceptability in all ages. Additionally, a combination treatment of Efavirenz and GSH can increase uptake and reduce cytotoxicity. There are many reports about the virus resistance of Efavirenz, but the Efavirenz is not reported to be used for resisting adenovirus.
The present invention evaluates efavirrenz for inhibitory activity against ADV7 virus.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and aims to provide an application of Efavirenz in preparing an anti-adenovirus ADV7 medicament, wherein the Efavirenz is used as an anti-ADV 7 virus screening compound, namely an application of a non-nucleoside reverse transcriptase inhibitor Efavirenz in preparing an anti-ADV 7 virus medicament.
In order to achieve the purpose, the invention provides an application of Efavirenz in preparing an anti-adenovirus ADV7 medicament. The method is characterized in that:
efavirenz has the following chemical structural formula (C) 14 H 9 ClF 3 NO 2 )。
Preferably, the maximum inhibition of the Hela cytopathic effect of ADV7 is 98% when efavirrenz is at 12.5 μ M.
Furthermore, the Efavirenz serving as an ADV7 virus inhibitor is added with pharmaceutically acceptable auxiliary materials and carriers and then used for preparing an anti-ADV 7 virus preparation.
Further, the preparation is any one of granules, tablets, pills, capsules or injections.
The invention has the following advantages and beneficial effects:
the object of the invention is achieved in that efavirrenz is tested for its activity by standard virus activity test methods.
According to the invention, through a large number of biological experiments, efavirenz is found to have the activity of resisting ADV7 virus. The specific expression is that the cell pathological effect caused by the ADV7 virus can be inhibited, the survival rate of infected cells is enhanced, the replication and proliferation of the ADV7 virus in the cells are inhibited, and the yield of progeny virus is reduced. Therefore, the compound has potential to prepare specific treatment medicines for resisting ADV7 infection and has a great clinical application prospect.
Drawings
FIG. 1 is a graph showing the effect of Efavirenz on Hela cell viability in response to ADV 7.
FIG. 2 shows the inhibitory effect of Efavirenz on CPE of Hela cells induced by ADV 7.
FIG. 3 shows the inhibitory effect of Efavirenz on the production of ADV7 progeny virus.
FIG. 4 shows the chemical structure of Efavirenz of the present invention.
Detailed Description
The technical solution of the present invention is further described in detail with reference to the accompanying drawings and specific embodiments.
The Efavirenz used in the present invention is from Shanghai ceramic Biotech Co., ltd.
The invention relates to an application of Efavirenz in preparing an ADV7 virus resistant medicament.
The application refers to that the Efavirenz is added with pharmaceutically acceptable auxiliary materials and carriers and is used for preparing the preparation for resisting the ADV7 virus.
The preparation is granule, tablet, pill, capsule, injection or dispersant.
The Efavirenz has the following chemical structural formula.
The application of the Efavirenz in resisting the ADV7 virus discovers that the Efavirenz has an obvious effect of resisting the ADV7 virus. Therefore, the compound has potential to prepare specific treatment medicines for resisting ADV7 infection and has a great clinical application prospect.
Example 1
The invention carries out an ADV7 activity resistant research experiment on the compound, and the experimental conditions are as follows: hereinafter, materials and operation methods used in the present invention are well known in the art, if not specifically described.
1. The test contents are as follows:
compound anti-ADV 7 activity assay: according to the invention, the activity of the Efavirenz against ADV7 is evaluated by combining a cytopathic effect analysis method and a cell survival rate detection method of MTT (methyl thiazolyl tetrazolium) determination.
2. The test method comprises the following steps:
2.1.1 toxicity of Compounds on host Hela cells
Hela cells were plated in 96-well plates at 37 ℃ with 5% CO 2 After the culture box is cultured to grow a full monolayer, cell culture solution is discarded, cell maintenance solutions containing test compounds with different concentrations are respectively added for continuous culture, the cytotoxicity is visually observed and respectively recorded by a microscope after 48 hours, and the cell survival rate is measured by an MTT method. The SPSS 11.5 software calculates the Median cytotoxic concentration (CC 50) of the drug for the cells. Cell survival rate = (drug group mean OD) 492 Value/cell control mean OD 492 Value) × 100%.
2.1.2 inhibitory Activity of Compounds on ADV7
Hela cells were plated in 96-well plates at 37 ℃ with 5% CO 2 Culturing in incubator until the culture medium grows to monolayer, discarding culture medium, and culturing at 100TCID 50 The ADV7 virus solution infected cells for 1.5h, and different concentrations of the test solution were addedCompound (ribavirin as a positive control drug) incubated cells. After the culture is continued for about 48 hours, the cytopathic effect (CPE) is observed under a microscope when about 90% of CPE lesions appear in the virus control wells. Observation and recording method of CPE: no cytopathic effect is recorded as-below 25% cytopathic effect, 25% -50% cytopathic effect is recorded as +++, 50% -75% cytopathic effect is recorded as +++, and more than 75% cytopathic effect is recorded as ++++.
After CPE observation is finished, the inhibition rate of the medicine on ADV7 is detected by using an MTT method. The method comprises the following specific steps: MTT 30. Mu.L (5 mg. Multidot.mL) was added to each well -1 ) After incubation for 3-4h, the supernatant was removed and 50. Mu.L of DMSO was added to dissolve the pellet. The absorbance (OD) at 492nm was read with a microplate reader 492 Value). The inhibition rate of the drug on ADV7 was calculated using the following formula.
The half effective Concentration of the drug (Concentration for 50%; maximum effect, EC50) was calculated using SPSS 11.5 software.
2.1.3 Therapeutic Index (TI) of drug
TI = CC50/EC50. A higher therapeutic index indicates greater antiviral potency.
3. Results of the experiment
TABLE 1Efavirenz cytotoxicity and anti-ADV 7 Activity
The results of the compound cytotoxicity and anti-ADV 7 activity tests are shown in table 1. The effect of compounds on Hela cell viability for ADV7 effects is shown in figure 1. The maximum inhibition rate of Efavirenz on the Hela cytopathic effect caused by ADV7 is 98% at 12.5 mu M.
Example 2
According to the invention, the activity of the compound against ADV7 is deeply researched, and an inhibitory effect test of the compound on the yield of ADV7 progeny viruses is implemented, wherein the test conditions are as follows:
1. content of the experiment
The inhibitory effect of the compounds on the production of ADV7 progeny virus was examined after infection of Hela cells with ADV7, respectively.
2. Test method
Hela cells in logarithmic growth phase are plated on a 24-well plate and grow into 100TCID after a monolayer 50 Cells were infected with ADV7, incubated at 37 ℃ for 1.5h, virus fluid removed, washed three times with PBS, and cell maintenance fluid containing compound at a concentration of 12.5. Mu.M was added. Collecting cells and supernatant culture solution after 48h, freeze thawing and lysing at-20 deg.C and 37 deg.C for three times, and collecting TCID 50 Methods determine ADV7 virus titers.
3. Test results
As shown in FIG. 3, the virus titer of the compound-treated Hela cells was significantly reduced compared to the virus control group, and was reduced by 4.2 logs relative to the virus control group.
In conclusion, efavirenz has stronger ADV7 activity inhibition, can inhibit Hela cell death caused by EV71, CVB3 and ADV7 viruses, and has potential to be prepared into a medicament for effectively resisting ADV7 infection in clinic.
Claims (4)
1. An application of Efavirenz in preparing an anti-adenovirus ADV7 medicament is characterized in that: the chemical structural formula of the compound Efavirenz with the activity of resisting ADV7 is as follows:
2. the use of efavirrenz according to claim 1 for the preparation of a medicament against adenovirus ADV7, wherein: the maximal inhibition of the ADV 7-induced Hela cytopathic effect was 98% when Efavirenz was at 12.5. Mu.M.
3. Use of efavirrenz according to claim 1 or 2 for the preparation of a medicament against adenovirus ADV7, wherein: the Efavirenz is used as an ADV7 virus inhibitor, and is added with pharmaceutically acceptable auxiliary materials and carriers to prepare an ADV7 virus resistant preparation.
4. The use of efavirrenz according to claim 3 for the preparation of a medicament against adenovirus ADV7, wherein: the preparation is any one of granules, tablets, pills, capsules or injections.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211742163.8A CN115957222A (en) | 2022-12-30 | 2022-12-30 | Application of Efavirenz in preparation of anti-adenovirus ADV7 drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211742163.8A CN115957222A (en) | 2022-12-30 | 2022-12-30 | Application of Efavirenz in preparation of anti-adenovirus ADV7 drugs |
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| Publication Number | Publication Date |
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| CN115957222A true CN115957222A (en) | 2023-04-14 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN202211742163.8A Pending CN115957222A (en) | 2022-12-30 | 2022-12-30 | Application of Efavirenz in preparation of anti-adenovirus ADV7 drugs |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130178517A1 (en) * | 2010-07-09 | 2013-07-11 | Richard L. Atkinson | Methods And Compositions For Treatment Of Lipogenic Virus Related Conditions |
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- 2022-12-30 CN CN202211742163.8A patent/CN115957222A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130178517A1 (en) * | 2010-07-09 | 2013-07-11 | Richard L. Atkinson | Methods And Compositions For Treatment Of Lipogenic Virus Related Conditions |
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