CN107904279A - A kind of screening technique of staphylococcus aureus inhibitor - Google Patents
A kind of screening technique of staphylococcus aureus inhibitor Download PDFInfo
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- CN107904279A CN107904279A CN201711071392.0A CN201711071392A CN107904279A CN 107904279 A CN107904279 A CN 107904279A CN 201711071392 A CN201711071392 A CN 201711071392A CN 107904279 A CN107904279 A CN 107904279A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/18—Testing for antimicrobial activity of a material
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/195—Assays involving biological materials from specific organisms or of a specific nature from bacteria
- G01N2333/305—Assays involving biological materials from specific organisms or of a specific nature from bacteria from Micrococcaceae (F)
- G01N2333/31—Assays involving biological materials from specific organisms or of a specific nature from bacteria from Micrococcaceae (F) from Staphylococcus (G)
Abstract
The invention belongs to biological technical field, and in particular to a kind of screening technique of staphylococcus aureus inhibitor.The screening technique includes the following steps：(1) candidate compound is obtained by virtual screening；(2) candidate compound for obtaining step (1) carries out the bacteriostatic activity test of staphylococcus aureus, obtains target compound.The screening technique of the present invention have found the compound for having inhibition to staphylococcus aureus and methicillin-resistant staphylococcus aureus.The method of the present invention greatlys save screening cost, has the advantages that the screening cycle is short, cost is low, high efficiency.Additionally there is selectivity, specificity and specificity.
Description
Technical field
The invention belongs to biological technical field, and in particular to a kind of screening technique of staphylococcus aureus inhibitor.
Background technology
Staphylococcus aureus (Staphylococcus aureus) is a kind of important pathogen of the mankind, is under the jurisdiction of Portugal
Grape Coccus (Staphylococcus), there is the nickname of " thermophilic meat bacterium ", is the representative of gram-positive bacteria, can cause many serious
Infection.Research shows that penicillin is obvious to staphylococcus aureus inhibitory action.This be primarily due to penicillin can suppress with
Aureus cell wall synthesizes relevant key enzyme.However, the generation of methicillin-resistant staphylococcus aureus makes green grass or young crops
The medicine of mycin class is entirely ineffective, also makes original target on the verge of being replaced.Therefore, modulation is selected, screens new suppression
Agent is extremely urgent.
Traditional inhibitor screening is directly to screen Staphylococcus aureus by paper disk method using different types of compound
The inhibitor of bacterium.The technology does not know the action target of medicine, mechanism of action, and heavy workload not only, and screening exists blindly
Property, screening cycle length is of high cost, and success rate is relatively low, such as a kind of " the golden yellow grape of Chinese patent 201510539676.2
Coccus inhibitor "-described in screening technique.
Threonyl tRNA synthetase is the key enzyme in protein synthesis, it is very conservative in same species, and not
But had differences with species.Therefore, threonyl tRNA synthetase is considered as the exploitation most promising target of bacterial inhibitor
One of.
At present, no document report is target sieving inhibitor using the threonyl tRNA synthetase of staphylococcus aureus,
More without document report with the virtual screening that the threonyl tRNA synthetase of staphylococcus aureus carries out and its new inhibitor
Exploitation.
The content of the invention
To solve the above-mentioned problems, present invention firstly provides a kind of screening technique of staphylococcus aureus inhibitor.
The present invention is achieved through the following technical solutions.
A kind of screening technique of staphylococcus aureus inhibitor, it is characterised in that the screening technique includes following step
Suddenly：
(1) candidate compound is obtained by virtual screening；
(2) candidate compound for obtaining step (1) carries out the bacteriostatic activity test of staphylococcus aureus, obtains target
Compound.
According to the present invention, in step (1), the virtual screening is preferably the virtual screening method of molecular docking.
According to the present invention, in step (1), the target that the virtual screening uses is staphylococcus aureus threonyl tRNA
Synzyme, such as staphylococcus aureus threonyl tRNA synthetase three-dimensional structure are albumen (the PDB ID in PDB：1NYR) or
The three-dimensional structure of other staphylococcus aureus threonyl tRNA synthetases.
According to the present invention, in step (1), also use positive control in the virtual screening, for example, using Boli mycin or
Positive control of the rifampin as virtual screening.
According to the present invention, in step (1), candidate compound is more than the compound of positive control for score, is preferably score
Compound more than before positive control and score rank 200,150 compound further preferably before ranking, such as before ranking 100 change
Compound.
According to the present invention, in step (2), the bacteriostatic experiment is selected from agar dilution, disk diffusion method or constant meat soup
Dilution method, is preferably disk diffusion method.
According to the present invention, in step (2), when bacteriostatic activity test uses disk diffusion method, target compound it is antibacterial
Circle is not less than 8mm, 9mm is preferably not less than, further preferably not less than 10mm.
As an implementation, screening technique of the present invention includes the following steps：
(S1.1) three-dimensional structure of staphylococcus aureus threonyl tRNA synthetase and the molecule of compound candidate are obtained
Structure；
(S1.2) structure of the step S1.1 three-dimensional structures obtained and compound candidate is subjected to molecular docking pre-treatment；
(S1.3) waited using the three-dimensional structure of step S1.2 processing and the structure of compound candidate by virtual screening
Select compound；
(S2) candidate compound obtained using step S1.3 carries out the bacteriostatic activity test of staphylococcus aureus.
Screening technique according to the present invention, in step S1.1,
The three-dimensional structure of staphylococcus aureus threonyl tRNA synthetase searches for acquisition, example preferably on the website of PDB
The three-dimensional structure that search obtains staphylococcus aureus threonyl tRNA synthetase such as on the website of PDB is the albumen in PDB
(PDB ID：1NYR) or other staphylococcus aureus threonyl tRNA synzyme three-dimensional structure.
The molecular structure of compound candidate preferably passes through the natural products data in compound database such as ZINC databases
Storehouse obtains, and can also be obtained by other compound databases, such as Pubmed Compound databases, the Specs of NCBI
The database for drug screening that database, drugbank databases or lark prestige company provide obtains.
The compound candidate can be small range compound library, such as that is downloaded from ZINC databases any contain
The small range compound library of 13000 compounds.
Screening technique according to the present invention, in step S1.2,
The docking pre-treating method uses discovery studio or VMD preferably before molecular docking
Any version of (Visual Molecular Dynamics) or AutoDockTools are to staphylococcus aureus threonyl
TRNA synzyme three-dimensional structure (PDB ID：1NYR) it is removed hydrone and/or removes substrate (including ATP, threonine and 2
Valency zinc ion) and/or the addition pre-treatment such as polarity hydrogen atom；Utilize open babel or discovery studio or VMD
(Visual Molecular Dynamics) or any version of AutoDockTools are added polarity to compound candidate
The pre-treatments such as hydrogen atom.
Preferably, the staphylococcus aureus threonyl tRNA synthetase three-dimensional structure and compound candidate are generated into lattice
Formula is pdbqt Three dimensional structure files.
Screening technique according to the present invention, in step S1.3, the software that the molecular docking uses can be AutoDock
Vina, also other molecular docking softwares can be used to be substituted, such as FlexX, 3D-Dock, Glide or GOLD therein
It is one or more.
Preferably, when being docked using AutoDock vina, its parameter size_x, size_y and size_z difference
It is set to 30 Ethylmercurichlorendimides, 30 Ethylmercurichlorendimides and 30 Ethylmercurichlorendimides, other specification acquiescence.
The present invention also provides the target compound that method as described above filters out to prepare suppression staphylococcus aureus medicine
Purposes in thing.
Preferably, when the target compound that the method is screened is a variety of, one or more therein can be selected
Combination prepares staphylococcus aureus inhibitor.
The present invention also provides a kind of method for suppressing staphylococcus aureus, it is characterised in that by a effective amount of as above institute
The target compound that the method for stating is screened acts on staphylococcus aureus.
The present invention also provides a kind of inhibitor, it is characterised in that the inhibitor includes screening to obtain by the method
Target compound, the inhibitor be used for suppress staphylococcus aureus.
The present invention also provides a kind of inhibitor, it is characterised in that the inhibitor includes screening to obtain by the method
Target compound, the inhibitor be used for suppress methicillin-resistant staphylococcus aureus.
The present invention also provides the compound that method as described above filters out to prepare methicillin-resistant staphylococcus aureus
Purposes in medicine.
Preferably, when the target compound that the method is screened is a variety of, one or more therein can be selected
Combination prepares methicillin-resistant staphylococcus aureus inhibitor.
The present invention also provides a kind of method for suppressing methicillin-resistant staphylococcus aureus, it is characterised in that the side
Method includes a effective amount of target compound acting on methicillin-resistant staphylococcus aureus.
Beneficial effects of the present invention：
1. by the screening technique of the present invention, have found to staphylococcus aureus and methicillin-resistant staphylococcus grape ball
Bacterium has the compound of inhibition.Methicillin-resistant staphylococcus aureus is that of obtaining the beta-lactam enzyme gene of external source, the base
Because the beta lactamase of expression can hydrolyze methicillin, make its failure.But the Soviet Union of methicillin-resistant staphylococcus aureus
Aminoacyl tRNA synthetase is identical with the threonyl tRNA synthetase of wild staphylococcus aureus not to occur any change
It is different, therefore since the inhibitor of threonyl tRNA synthetase has effect to wild-type S. aureus bacterium, so as to resistance to methoxy
Staphylococcus aureus has effect in XiLin.Due to the present invention method greatly save screening cost, have screening the cycle it is short, into
The advantages that this is low, high efficiency.
2. the target of the Screening target that the screening technique of the present invention uses and staphylococcus aureus inhibitor screening before
It is different.The screening technique of the present invention is that the virtual screening based on molecular docking is combined with bacteriostatic experiment, with traditional golden yellow Portugal
Grape coccus inhibitor screening method is different.
3. the compound that the screening technique of the present invention obtains has staphylococcus aureus inhibitory action, and to Escherichia coli
Unrestraint acts on, and the resistance to the action of a drug for efficiently solving staphylococcus aureus and methicillin-resistant staphylococcus aureus generation is asked
Topic.
4. the compound that method of the invention filters out is to suppressing staphylococcus aureus with selective, specific and special
One property.This is because the amino of Escherichia coli threonyl tRNA synthetase and staphylococcus aureus threonyl tRNA synthetase
Acid composition and protein three-dimensional structure are different.The present inventor using staphylococcus aureus threonyl tRNA synthetase as target,
Screen obtained inhibitor and only suppress staphylococcus aureus, without suppressing Escherichia coli, illustrate the suppression that the present inventor filters out
Preparation has selectivity, specificity and specificity.The screening technique of the further explanation present invention is efficient, is that one kind has very big answer
With value and the method for great application prospect.
Brief description of the drawings
Fig. 1 is the flow chart of 1 screening technique of embodiment.
1-5 is fungistatic effects of the compound 1-5 to Escherichia coli ATCC25922 in 2A in Fig. 2 Fig. 2；1-5 in 2B in Fig. 2
Fungistatic effect for compound 6-10 to Escherichia coli ATCC25922；1-5 is compound 11-15 to Escherichia coli in 2C in Fig. 2
The fungistatic effect of ATCC25922；1-5 is fungistatic effects of the compound 16-20 to Escherichia coli ATCC25922 in 2D in Fig. 2；Figure
1-5 is fungistatic effects of the compound 21-25 to Escherichia coli ATCC25922 in 2E in 2；1-5 is compound 26- in 2F in Fig. 2
The fungistatic effect of 30 couples of Escherichia coli ATCC25922；1-5 is compound 31-35 to Escherichia coli in 25922G in Fig. 2
The fungistatic effect of ATCC25922,6 fungistatic effect for Boli mycin to Escherichia coli ATCC25922, L is methanol to large intestine bar
The fungistatic effect of bacterium ATCC25922.1-5 is compound 1-5 to the antibacterial of staphylococcus aureus ATCC6538 in 6A in Fig. 2
Effect；1-5 is fungistatic effects of the compound 6-10 to staphylococcus aureus ATCC6538 in 6B in Fig. 2；1-5 in 6C in Fig. 2
Fungistatic effect for compound 11-15 to staphylococcus aureus ATCC6538；1-5 is 16-20 pairs of compound in 6D in Fig. 2
The fungistatic effect of staphylococcus aureus ATCC6538；1-5 is compound 21-25 to staphylococcus aureus in 6E in Fig. 2
The fungistatic effect of ATCC6538；1-5 is antibacterial effects of the compound 26-30 to staphylococcus aureus ATCC6538 in 6F in Fig. 2
Fruit；In Fig. 2 in 6538G 1-5 for compound 31-35 to the fungistatic effect of staphylococcus aureus ATCC6538,6 be rifampin
To the fungistatic effect of staphylococcus aureus ATCC6538, L is antibacterial effect of the methanol to staphylococcus aureus ATCC6538
Fruit.
Fig. 3 is the structural formula of 35 kinds of candidate compounds of 1 purchase in embodiment.
Embodiment
Further detailed description is done to the screening technique of the present invention below in conjunction with specific embodiment.It should be appreciated that
The following example is merely illustrative the ground description and interpretation present invention, and is not necessarily to be construed as limiting the scope of the invention.
In the range of all technologies realized based on the above of the present invention are encompassed by it is contemplated that protecting.
Unless otherwise indicated, the raw materials and reagents used in following embodiments is commercial goods, or can be by
It is prepared by perception method.
Embodiment 1
Experimental design：
It is starting with small range compound library (about 13000 compounds), carries out structure-based virtual screening, and carry out
Bacteriostatic activity test is verified, to obtain active inhibitor within the shortest time.
Concrete operations：
(1) acquisition of ZINC databases
ZINC databases be one be used for ligand screening free public resource (J.J.Irwin, T.Sterling,
M.M.Mysinger,E.S.Bolstad,&R.G.Coleman,2012).Log in ZINC website (http://
Zinc.docking.org), into interface is downloaded, all commercially available n-compounds are downloaded, amount to 22724825 kinds of (cut-offs
To the fund applying date).The compound of download is presented in the form of multiple compressed files, and each file contains about 13000 kinds of chemical combination
Thing.One of small range compound library compressed file is optionally taken to be used for structure-based virtual screening.
(2) it is based on the virtual screening of staphylococcus aureus threonyl tRNA synthetase (SAThrRS) structure
A. the acquisition of target construction
From protein data bank (PDB) (P.W.Rose, AA Altunkaya,C.Bi,A.R.
Bradley, C.H.Christie, L.D.Costanzo, J.M.Duarte, et al., 2016) website (http://
Www.rcsb.org/pdb/home/home.do Three dimensional structure files (the PDB ID for downloading SAThrRS are searched on)：1NYR)
(Alfredo Torres-Larios,Rajan Sankaranarayanan,Bernard Rees,Anne-Catherine
Dock-Bregeon , ＆Dino Moras, 2003), the target as inhibitor screening.
B. the virtual screening based on molecular docking
Using molecular docking technology, the small range compound library that SAThrRS and step (1) are obtained carries out virtual screening.
The software of molecular docking is AutoDock Vina (O.Trott＆A.J.Olson, 2010).Before carrying out virtual screening, use
AutoDockTools(G.M.Morris,R.Huey,W.Lindstrom,M. F.Sanner,R.K.Belew,
D.S.Goodsell ,s ＆A.J.Olson, 2009) it is pdbqt by the format conversion of SAThrRS Three dimensional structure files, uses open
babel(Noel M.O'Boyle,Michael Banck, Craig A.James,Chris Morley,Tim
Vandermeersch, ＆Geoffrey R.Hutchison, 2011) every kind of small molecule in compound library is generated pair respectively
The Three dimensional structure files answered, form pdbqt.Docking center is the aminoacyl chain carrier of SAThrRS, i.e. ATP and Soviet Union's ammonia
Position where sour.Docking scope isBoli mycin is used for virtual screening as positive control, obtains
Score is more than 100 candidate compounds before Boli mycin and score rank.35 compounds therein are bought, this 35 candidate compounds
The structure of thing is as shown in Figure 3.
(3) bacteriostatic activity test
A. the purchase of candidate compound is prepared with susceptibility piece
Buy ranking before 100 and score be more than Boli mycin micromolecular compound in 35 compounds.With 50% first
Alcohol water dissolves every kind of compound, final concentration of 1mg/mL, 0.22 μm of sterile filtering with microporous membrane respectively.Using filter paper punching certainly
A diameter of 6mm susceptibility pieces are made, infiltrate the several seconds in sterile centrifugation tube of the input equipped with filtrate after sterilizing, it is sterile to take out susceptibility piece loading
Centrifuge tube, sterile brown paper is properly wrapped up to be dried for standby in 50 DEG C of baking ovens of postposition.
B. the preparation of bacteria suspension
Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 25922 are inoculated in fresh meat soup culture respectively
Base, puts 37 DEG C of 20~24h of constant temperature incubation in incubator, and the method for plate culture count (Li Erwei, 2010) counts the viable count of 2 kinds of bacterium.
C. the measure of bacteriostatic activity
Using disk diffusion method (KB), a diameter of 90mm sterilized petri dishes are taken, add the plain agar culture medium that heat is melted
30mL, lies in a horizontal plane in vaccination station and solidifies.Take 100 μ L staphylococcus aureuses ATCC 6538 or Escherichia coli ATCC
25922 are spread evenly across agar plate surface, and after tablet moisture drying, tablet is attached to aseptic nipper gripping drug sensitive test paper
On, each tablet glues 5 scraps of paper, spreads 15min, is inverted 37 DEG C of constant temperature incubation 24h in the incubator, the candidate that will be commercially available
Compound sets 3 repetitions, measures antibacterial circle diameter.Judge that extract is antibacterial according to inhibition zone and antibacterial circle diameter size is whether there is
Effect.The results are shown in Figure 2.From the result of Fig. 2, wherein there have 9 compounds to have staphylococcus aureus to be preferable
Inhibition.
In addition, it can be seen that in this contrast bacteriostatic experiment of 35 candidate compounds to Escherichia coli ATCC 25922
The target compound that method as described above filters out has selectivity, specificity to suppressing staphylococcus aureus ATCC6538
And specificity, and preferable inhibition is not shown to Escherichia coli ATCC 25922.
More than, embodiments of the present invention are illustrated.But the present invention is not limited to the above embodiment.It is all
Within the spirit and principles in the present invention, any modification, equivalent substitution, improvement and etc. done, should be included in the guarantor of the present invention
Within the scope of shield.
Claims (10)
1. a kind of screening technique of staphylococcus aureus inhibitor, it is characterised in that the screening technique includes the following steps：
(1) candidate compound is obtained by virtual screening；
(2) candidate compound for obtaining step (1) carries out the bacteriostatic activity test of staphylococcus aureus, obtains target chemical combination
Thing.
2. the screening technique of staphylococcus aureus inhibitor described in claim 1, it is characterised in that in step (1), the void
Intend the virtual screening method that screening is preferably molecular docking；
Preferably, in step (1), the target that the virtual screening uses is staphylococcus aureus threonyl tRNA synthetase,
Such as staphylococcus aureus threonyl tRNA synthetase three-dimensional structure is albumen (the PDB ID in PDB：1NYR) or other gold
The three-dimensional structure of staphylococcus aureus threonyl tRNA synthetase；
Preferably, in step (1), positive control is also used in the virtual screening, such as make using Boli mycin or rifampin
For the positive control of virtual screening；
Preferably, in step (1), candidate compound is more than the compound of positive control for score, is also preferably that score is more than sun
Property control and score rank before 200 compound, 100 compound before 150 compound further preferably before ranking, such as ranking.
3. the screening technique of the staphylococcus aureus inhibitor of claim 1 or 2, it is characterised in that in step (2), institute
State bacteriostatic experiment and be selected from agar dilution, disk diffusion method or constant broth dilution method, be preferably disk diffusion method；
Preferably, when bacteriostatic activity test uses disk diffusion method, the inhibition zone of target compound is not less than 8mm, preferably not
Less than 9mm, further preferably not less than 10mm.
4. the screening technique of any one of the claim 1-3 staphylococcus aureus inhibitor, it is characterised in that the method
Include the following steps：
(S1.1) three-dimensional structure of staphylococcus aureus threonyl tRNA synthetase and the molecular structure of compound candidate are obtained；
(S1.2) structure of the step S1.1 three-dimensional structures obtained and compound candidate is subjected to molecular docking pre-treatment；
(S1.3) obtained using the three-dimensional structure of step S1.2 processing and the structure of compound candidate by virtual screening candidates
Compound；
(S2) candidate compound obtained using step S1.3 carries out the bacteriostatic activity test of staphylococcus aureus.
5. the screening technique of any one of the claim 1-4 staphylococcus aureus inhibitor, it is characterised in that step S1.1
In, the three-dimensional structure of staphylococcus aureus threonyl tRNA synthetase searches for acquisition preferably on the website of PDB, such as
The three-dimensional structure that search obtains staphylococcus aureus threonyl tRNA synthetase on the website of PDB is the albumen (PDB in PDB
ID：1NYR) or other staphylococcus aureus threonyl tRNA synthetases three-dimensional structure；
Preferably, the molecular structure of compound candidate preferably passes through the natural products number in compound database such as ZINC databases
Obtain, can also be obtained by other compound databases according to storehouse, such as the Pubmed Compound databases of NCBI,
The database for drug screening that Specs databases, drugbank databases or lark prestige company provide obtains；
Preferably, the compound candidate can be small range compound library, such as that is downloaded from ZINC databases any contain
There is the small range compound library of 13000 compounds.
6. the screening technique of any one of the claim 1-5 staphylococcus aureus inhibitor, it is characterised in that step S1.2
In,
The docking pre-treating method uses discovery studio or VMD (Visual preferably before molecular docking
Molecular Dynamics) or AutoDockTools any version to staphylococcus aureus threonyl tRNA synthetase
Three-dimensional structure (PDB ID：1NYR) it is removed hydrone and/or removes substrate (including ATP, threonine and divalent zinc ion)
And/or the pre-treatment such as addition polarity hydrogen atom；Utilize open babel or discovery studio or VMD (Visual
Molecular Dynamics) or any version of AutoDockTools polarity hydrogen atom etc. is added to compound candidate
Pre-treatment；
Preferably, it is by the staphylococcus aureus threonyl tRNA synthetase three-dimensional structure and compound candidate generation form
Pdbqt Three dimensional structure files.
7. the screening technique of any one of the claim 1-6 staphylococcus aureus inhibitor, it is characterised in that step S1.3
In, the software that the molecular docking uses can be AutoDock vina, also other molecular docking softwares can be used to be replaced
Generation, such as FlexX, 3D-Dock, Glide or GOLD one or more therein；
Preferably, when being docked using AutoDock vina, its parameter size_x, size_y and size_z are set to
30 Ethylmercurichlorendimides, 30 Ethylmercurichlorendimides and 30 Ethylmercurichlorendimides, other specification acquiescence.
8. the target compound that the screening technique of any one of the claim 1-7 staphylococcus aureus inhibitor filters out exists
Prepare the purposes suppressed in staphylococcus aureus medicine；
Preferably, when the target compound that the method is screened is a variety of, one or more combinations therein can be selected
Prepare staphylococcus aureus inhibitor.
9. the present invention also provides a kind of inhibitor, it is characterised in that the inhibitor is included by any one of claim 1-7 institute
The target compound that the screening technique of staphylococcus aureus inhibitor screens is stated, the inhibitor is used to suppress golden yellow
Staphylococcus or methicillin-resistant staphylococcus aureus.
10. the compound that the screening technique of any one of the claim 1-7 staphylococcus aureus inhibitor filters out is being made
Purposes in standby methicillin-resistant staphylococcus aureus medicine.
Preferably, when the target compound that the method is screened is a variety of, one or more combinations therein can be selected
Prepare methicillin-resistant staphylococcus aureus inhibitor.
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| WO2019085806A1 (en) * | 2017-11-03 | 2019-05-09 | 中国农业科学院北京畜牧兽医研究所 | Screening method for staphylococcus aureus inhibitor |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019085806A1 (en) * | 2017-11-03 | 2019-05-09 | 中国农业科学院北京畜牧兽医研究所 | Screening method for staphylococcus aureus inhibitor |
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