CN106511346A - Small molecular drug capable of being used for inhibiting Zika virus infection and application of drug - Google Patents

Small molecular drug capable of being used for inhibiting Zika virus infection and application of drug Download PDF

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Publication number
CN106511346A
CN106511346A CN201611121927.6A CN201611121927A CN106511346A CN 106511346 A CN106511346 A CN 106511346A CN 201611121927 A CN201611121927 A CN 201611121927A CN 106511346 A CN106511346 A CN 106511346A
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menglusitena
zika virus
virus infection
medicine
zikv
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邹鹏
陆路
姜世勃
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SHANGHAI PUBLIC HEALTH CLINICAL CENTER
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SHANGHAI PUBLIC HEALTH CLINICAL CENTER
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Priority to CN201611121927.6A priority Critical patent/CN106511346A/en
Publication of CN106511346A publication Critical patent/CN106511346A/en
Priority to CN201710249081.2A priority patent/CN106983750A/en
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    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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

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  • 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)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention belongs to the technical field of biological medicines and particularly relates to a small molecular drug capable of being used for inhibiting Zika virus infection and an application of the drug, in particular to a method for inhibiting Zika virus infection through Montelukast sodium and an application of Montelukast sodium in preparation of drugs for preventing and/or treating symptoms or diseases related to Zika virus infection.

Description

A kind of small-molecule drug and its application that can be used to suppress zika virus infection
Technical field
The invention belongs to biotechnology, biomedicine technical field, especially relate to one kind and can be used to suppress stockaded village's card disease The small-molecule drug of poison infection and its application.
Background technology
Zika virus (Zika virus, ZIKV) belongs to flaviviridae Flavivirus, the icosahedron with envelope protein Virus.Its genome is a positive single stranded RNA, has about 10800 nucleotide, 3 structural protein of coding (PrM, Env, Capsid) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5).ZIKV is in arbovirus Kind, propagation is bitten by diurnal yellow-fever mosquito mainly, but its circulation way also has vertical transmission, spreads through sex intercourse and biography of transfusing blood Broadcast.
First plant of ZIKV is in Rhesus Macacus of the nineteen forty-seven in stockaded village of Uganda Carson woods by isolated first, the second strain virus It is isolated in white line speckle mosquito (Aedes.Africanus) in areal in 1948.Before 2007, only occurs people once in a while Class cases of infection.In April, 2007, ZIKV the first explosions on YAP (Yap) island of Western Pacific Micronesia occur 49 Example ZIKV infection confirmed cases, 59 ZIKV infect suspected case.- 2014 years 2013, ZIKV was in French Polynesia, multiple Movable joint archipelago, the Cook Islands, new Scotland outbreak of epidemic again.In April, 2015 causes (2016 5 at present in the outburst of Brazil Months 18 days) there is the infection of ZIKV in 60, whole world countries.
ZIKV infection causes the symptoms such as fever, measles, arthralgia, myalgia, headache and conjunctivitis, but more than symptom compared with Gently, it is self-limited disease, voluntarily takes a turn for the better after general 2～7 days.Lasting semelincident immunization can be obtained after people's infection, currently without The report of subinfection again after infection.
But after having proven to ZIKV infection anemia of pregnant woman at present, virus can penetrate placental barrier, or baby can be caused microcephaly occur Disease or other than more serious brain injury, especially at first 3 months of pregnancy.Meanwhile, ZIKV infection may also with Ji Lan-Ba Lei (Guillain-Barre) syndrome is relevant.
However, the vaccine that not yet effectively prevention and/or treatment ZIKV infect in the world at present or medicine, prevention ZIKV infection Major measure be to prevent biting for mosquito, and to ZIKV infection treatment be symptomatic treatment, alleviate its disease symptoms.So urgently The specific medicament for ZIKV need to be studied, it is desirable to be able to which the anemia of pregnant woman to infect ZIKV provides specific treatment, to reduce microcephaly The birth of baby, and also to prevent from preventing and/or treat Guillain-Barre＆1＆ syndrome.
The content of the invention
It is an object of the invention to provide one kind can suppress the small-molecule drug that zika virus (ZIKV) infects, so as to reality Prevention now to ZIKV infection and/treatment.
In a first aspect, the invention provides it is a kind of suppress zika virus infection method, including the Meng for giving effective dose Montelukast sodium.
In second aspect, the invention provides Menglusitena is in the medicine for suppressing zika virus infection is prepared Purposes.
In the third aspect, the invention provides Menglusitena is being prepared for treating and/or preventing zika virus to infect Purposes in the medicine of associated conditions or disease.
By using Menglusitena, either on a cellular level or in animal level, ZIKV infection can be with It is effectively suppressed.Toxicity test result displays that Menglusitena does not have overt toxicity to cell simultaneously.
Description of the drawings
Fig. 1 illustrates that Menglusitena infects the suppression of BHK21 cells and Vero cells to ZIKV strains SZ01；Can from figure To find out, Menglusitena can effectively suppress infection of the SZ01 to BHK21 cells and Vero cells, IC50 values respectively may be about 0.33 μM and 1.21 μM.
Fig. 2 illustrates that Menglusitena infects the suppression of BHK21 cells and Vero cells to ZIKV strains FLR；Can from figure To find out, Menglusitena can effectively suppress infection of the FLR to BHK21 cells and Vero cells, IC50 values respectively may be about 2.45 μM and 2.96 μM.
Fig. 3 illustrates that Menglusitena infects the suppression of BHK21 cells and Vero cells to ZIKV strains MR766；From figure As can be seen that Menglusitena can effectively suppress infection of the MR766 to BHK21 cells and Vero cells, IC50 values are respectively about For 1.78 μM and 1.92 μM.
Fig. 4 illustrates toxicity of the Menglusitena to BHK21 cells；It can be seen that Menglusitena is without obvious poison Property, its half toxic concentration CC50>20000nM.
Fig. 5 illustrates suppression of the Menglusitena to AG6 mouse infection ZIKV strain SZ01；It can be seen that with Vehicle (DMSO) is compared, and Menglusitena is obviously improved the survival rate of AG6 mices.
Specific embodiment
Further clear and complete description is made to the concrete technical scheme of the present invention below by Examples below.Need It is understood that the technical scheme for hereinafter specifically describing is only for the purposes of illustration, it is not intended that by any way to the present invention's Protection domain is limited.In the case of the spirit and objective without departing substantially from the present invention, technical scheme can be entered Row modification.Protection scope of the present invention is defined by appended claims.
As described above, it is an object of the invention to provide one kind can suppress the small molecule medicine that zika virus (ZIKV) infects Thing, so as to realize the prevention to ZIKV infection and/treatment.
For achieving the above object, the present inventor has carried out screening operation based on small-molecule drug storehouse, it is therefore an objective to screen Go out with the small molecule for suppressing ZIKV virus activities, for the prevention infected to ZIKV and/or treatment.Jing is screened, the present inventor It was unexpectedly observed that Menglusitena shows the activity of good and special suppression ZIKV.
Specifically, the present inventor have studied Menglusitena first on a cellular level to several ZIKV virus strain infections The inhibitory action of BHK21 and Vero cells, as a result finds that the medicine can effectively suppress the activity of ZIKV, wherein suppressing strain SZ01 respectively may be about 0.33 μM and 1.21 μM to the half-inhibition concentration IC50 of BHK21 cells and Vero cell infections, suppress poison Strain FLR respectively may be about 2.45 μM and 2.96 μM to the IC50 of BHK21 cells and Vero cell infections, suppress strain MR766 pair The IC50 of BHK21 cells and Vero cell infections respectively may be about 1.78 μM and 1.92 μM.
Secondly, the present inventor also have studied inhibitory action of the Menglusitena to ZIKV in animal level, as a result find Menglusitena is also inhibited to SZ01 virus strain infections AG6 mices, can be obviously improved the survival rate of AG6 mices.
In addition, the present inventors have additionally discovered that, Menglusitena does not have obvious cytotoxicity.In the present invention, inventor with The cytotoxicity of Menglusitena is verified as a example by BHK21 cells, as a result find which to cell without overt toxicity, half Toxic concentration CC50>20000nM.Therefore, Menglusitena has preferable safety.
Based on more than find, the present inventor thus reached this application claims invention.
Before describing the invention in detail, first Menglusitena is briefly described.
The English entitled Montelukast sodium of Menglusitena, its molecular formula are C35H35ClNO3S Na, chemistry Structural formula is as follows：
Menglusitena is currently the medicine that a kind of FDA ratifies for clinical treatment asthma and allergic rhinitises, is Oral LTRA, energy specificity suppress cysteinyl leukotriene (CysLT1) receptor in air flue, improve gas Road inflammation, effective control symptoms of asthma.Menglusitena is B in Hazard rank classification of the medicine that FDA is formulated to gestation Class, with preferable safety, and which also has reduction neuroinflamation document report, lifts hippocampal neural and occurs, improves The effect of geriatric animals learning and memory.
Therefore, in a first aspect, the invention provides a kind of method for suppressing zika virus infection, including giving effective dose Menglusitena.
Methods described directly can be implemented on animal body or human body, for directly suppressing zika virus, and then realize The prevention and/or treatment of associated conditions or disease are infected to zika virus.Methods described can also be in tissue or cellular level Upper enforcement, for the purpose for for example carrying out scientific research.In other words, methods described can be implemented for preventing purpose and/or controlling Treat purpose, it is also possible to implement for non-prevention purpose and/or non-treatment purpose.
Term " effective dose " as used herein refers to that Menglusitena can effectively suppress the amount that zika virus infects.This Art personnel can determine the effective dose according to factors such as experimental subject, experiment purpose, administering modes.
In second aspect, the invention provides Menglusitena is in the medicine for suppressing zika virus infection is prepared Purposes.
In one embodiment, Menglusitena is combined described for suppressing zika virus for preparing with other medicines The medicine of infection.
The other medicines can be that for example, Enbrel card gives birth to (emricasan), -2 '-C- methyladenosine (7- of 7- denitrifications Deaza-2 '-C-methyladenosine, 7-deaza-2 '-CMA), 2 '-C- methyladenosine (2 '-C- Methyladenosine, 2 '-CMA), 2'CmeC (2 '-C-methylcytidine, 2 '-CMC), 2 '-C- methyl birds Glycosides (2 '-C-methylguanosine, 2 '-CMG), 2 '-C- methyluridines (2 '-C-methyluridine, 2 '-CMU), (-)- Epigallocatechin gallate (EGCG) ((-)-epigallocatechin gallate, EGCG), niclosamide , but not limited to this (Niclosamide).
In the third aspect, the invention provides Menglusitena is being prepared for treating and/or preventing zika virus to infect Purposes in the medicine of associated conditions or disease.
In one embodiment, zika virus infection associated conditions or disease be zika virus infection cause it is little Head disease or Guillain-Barre＆1＆ syndrome.
Herein, when addressing for treating and/or preventing zika virus to infect the microcephaly for causing, referring to will be effective The medicine of amount directly gives the anemia of pregnant woman of zika virus infection, so as to treat indirectly the suffered from microcephaly of anemia of pregnant woman foetus And/or prevent fetus to suffer from microcephaly indirectly.
Microcephaly refers to head much smaller than other of the same age and same sex baby head newborn teratogenesis.If with brain development not Good, microcephaly baby might have dysplasia.Microcephaly is from slightly to seriously.Cause microcephaly there be many originals Cause, infects including zika virus.
But Guillain-Barre＆1＆ syndrome is a kind of rarely found very serious disease, is frequently experienced in virus or antibacterial sense In a few days to a few weeks after dye, serious nerve injury, common sympton can be caused to include muscle weakness, pain, sense organ obstacle, Paralysis can be caused in the case of quite serious.Guillain-Barre＆1＆ syndrome be with the Demyelination of peripheral nerve and nerve root and Autoimmunity peripheral neuropathy of the thin vessels inflammatory cell infiltration for pathological characteristic, classic Guillain-Barre＆1＆ syndrome quilt Referred to as Guillain Barre syndrome (AIDP), clinical manifestation are the flaccid quadriplegia of acute symmetry.
In one embodiment, Menglusitena is combined described for suppressing zika virus for preparing with other medicines The medicine of infection.
The other medicines can be, for example, the life of Enbrel card, -2 '-C- methyladenosines of 7- denitrifications, 2 '-C- methyladenosines, 2'CmeC, 2 '-C- methylguanosines, 2 '-C- methyluridines, (-)-epigallocatechin gallate (EGCG) or chlorine nitre Willow amine, but not limited to this.
The application test result indicate that, either on a cellular level or in animal level, Menglusitena Effectively to suppress zika virus to infect.Toxicity test result is also shown that Menglusitena does not have overt toxicity to cell simultaneously. Therefore, it is possible to use Menglusitena suppresses zika virus infection, and then prevent and/or treat zika virus infection associated conditions Or disease.
Embodiment
The suppression in vitro to ZIKV infection of 1. Menglusitena of embodiment
Menglusitena suppresses the experimental implementation of ZIKV infection to may be referred to document：Zhiwu Sun,et al., Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection；Viruses 2015,7,798-819；doi:10.3390/v7020798, it is specific as follows：
(1) ZIKV was separated from 38 years old in Chinese male patient's body, and by isolated ZIKV by being inoculated with C6/36 cells Expanded (Sci China Life Sci, doi:10.1007/s11427-016-5043-4).
(2) using serum-free DMEM in 96 orifice plates gradient dilution Menglusitena so as to concentration be respectively 10 μM, 5 μM, 2.5 μM, 1.25 μM, 0.625 μM, 0.3125 μM, 0.156 μM, 0.078 μM, be 50 μ L per hole dosing volume, each concentration setting 3 repetitions.
(3) using serum-free DMEM dilution ZIKV (strain is respectively SZ01, MR766, FLR) so that the final concentration of ZIKV For 3TCID50 (tissue culture infective dose), ZIKV is added according to the amount of 50 μ L of every hole 96 orifice plates in (2), while Arrange the positive of virus infection to organize and virus-free negative group without medicine.Virus with 37 DEG C of medicine under the conditions of incubation 1 hour 30 points Clock.
(4) using EDTA-EGTA Digestive systems digestion process BHK21 or Vero cells, should using the DMEM containing 2%FBS Cell is diluted to 2*105/ mL, and 96 orifice plates in (3) are added by the amount in 100 μ L/ holes.Afterwards in 37 DEG C, 5%CO2Under the conditions of train Support.
(5) when causing complete cell death to the obvious CPE (CPE) of positive group cell appearance, using CCK8 Inhibitory activity of the detection Menglusitena to virus.The concrete operations of CCK8 detections are as follows：
A) culture medium abandoned in 96 orifice plates is carefully inhaled, the fresh DMEM containing 2%FBS is added, continues culture 2-4 hours.
B) 1mL CCK8 solution is added in DMEM of the 9mL containing 2%FBS (consumption of one piece of 96 orifice plate), overturns and mix, obtain To CCK8 reactant liquors.
C) culture medium abandoned in 96 orifice plates is carefully inhaled, the CCK8 reactant liquors described in b) is added in 96 holes, per 100 μ of hole L。
D) cultivate 1 hour under the conditions of 37 DEG C, determine the OD in each hole afterwards in microplate reader450Absorbance.
(6) inhibitory activity of Menglusitena is calculated, the formula for using is：The inhibitory activity of Menglusitena=(AMedicine hole- AViral hole)*100/(AWithout medicine hole-AViral hole), wherein AMedicine holeRefer to the absorbance in the hole containing medicine, virus, cell and CCK8, AViral hole Refer to the absorbance in the hole containing virus, cell and CCK8, AWithout medicine holeRefer to that the hole for comprising only cell and CCK8 is (disease-free without medicine Poison) hole absorbance.
Inhibition test result shows：Menglusitena can preferably suppress the infection of ZIKV, suppress strain SZ01 pair The half-inhibition concentration IC50 of BHK21 cells and Vero cell infections respectively may be about 0.33 μM and 1.21 μM (Fig. 1)；Suppress strain FLR respectively may be about 2.45 μM and 2.96 μM (Fig. 2) to the IC50 of BHK21 cells and Vero cell infections；Suppress strain MR766 pair The IC50 of BHK21 cells and Vero cell infections respectively may be about 1.78 μM and 1.92 μM (Fig. 3).
Toxicity detection of 2 Menglusitena of embodiment to BHK21 cells
Toxicity detection operation of the Menglusitena to BHK21 cells may be referred to document：Zhiwu Sun,et al., Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection.Viruses 2015,7,798-819；doi:10.3390/v7020798), it is specific as follows：
(1) using serum-free DMEM dilute Menglusitena so as to concentration be respectively 20 μM, 10 μM, 5 μM, 2.5 μM, 1.25 μM, 0.625 μM, 0.3125 μM, 0.156 μM, be 100 μ L per hole dosing volume, each concentration 2 repetition of setting.
(2) using EDTA-EGTA Digestive system digestion process BHK21 cells, cell is diluted using the DMEM containing 2%FBS For 4*105/ mL, and 96 orifice plates in (1) are added by the amount in 100 μ L/ holes.Afterwards in 37 DEG C, 5%CO2Under the conditions of cultivate 4 days.
(3) culture medium abandoned in 96 orifice plates is carefully inhaled, the fresh DMEM containing 2%FBS is added, continues culture 2-4 hours.
(4) 1mL CCK8 solution is added in DMEM of the 9mL containing 2%FBS (consumption of one piece of 96 orifice plate), overturns and mix, Obtain CCK8 reactant liquors.
(5) culture medium abandoned in 96 orifice plates is carefully inhaled, the CCK8 reactant liquors described in (4) is added in 96 holes, per hole 100 μL。
(6) 37 DEG C, 5%CO2Under the conditions of cultivate 1 hour, determine the OD in each hole afterwards in microplate reader450Absorbance.
(7) activity of cell is calculated, the computational methods for using are：Cytoactive=(AMedicine hole-AAcellular hole)*100/(AWithout medicine hole- AAcellular hole), wherein AMedicine holeRefer to the absorbance in the hole containing medicine, cell and CCK8, AAcellular holeRefer to not drug containing and cell, only The absorbance in the hole containing CCK8, AWithout medicine holeRefer to not drug containing, containing only cell and the absorbance in the hole of CCK8.
Toxicity test result shows：Menglusitena to BHK21 cells without overt toxicity, its half toxic concentration CC50> 20000nM (Fig. 4).
Suppression of 3. Menglusitena of embodiment in mouse model to ZIKV infection
Menglusitena is carried out as follows to the Inhibition test of ZIKV infection in mouse model：
(1) 20 AG6 mices are divided into into two groups (medicine group and matched groups), 10 per group, medicine group is with 45mg/kg abdominal cavities Drug administration by injection, matched group lumbar injection DMSO.
After (2) 8 hours, the SZ01 of every AG6 mouse peritoneal injection 1000PFU (plaque forming unit) is viral.Virus note Shoot away after finishing, medicine group is with 45mg/kg intraperitoneal injections, matched group lumbar injection DMSO.
(3) medicine group is administered for continuous 7 days in the same manner, and matched group injects DMSO for continuous 7 days in the same manner, and daily Observation mouse survival rate.
Mouse model inhibition test result shows：Menglusitena can preferably suppress ZIKV strain SZ01 little to AG6 The infection of Mus, from figure 5 it can be seen that compared with Vehicle (DMSO), Menglusitena is obviously improved the existence of AG6 mices Rate.
It is obvious to the skilled person that the present invention is not limited to the details of above-mentioned example, not In the case of the spirit and objective of the present invention, those skilled in the art are it is conceivable that the change of technical scheme described herein Scheme, and the change programme is also within the scope of the present invention.Protection scope of the present invention is limited by appended claims It is fixed.
Although in addition, it will be appreciated that this specification by embodiment come invention has been described, it is not every Individual embodiment only includes an independent technical scheme.This narration scheme of this specification only for clarity, this area Technical staff should be by this specification as an entirety, and the technical scheme in each embodiment can be formed with appropriately combined It will be appreciated by those skilled in the art that other embodiment.

Claims (8)

1. a kind of method that suppression zika virus infects, including the Menglusitena for giving effective dose.
2. Menglusitena is used to suppress the purposes in the medicine of zika virus infection in preparation.
3. purposes according to claim 2, wherein Menglusitena are combined described for pressing down for preparing with other medicines The medicine of zika virus infection processed.
4. the purposes described in claim 3, wherein the other medicines be the life of Enbrel card, -2 '-C- methyladenosines of 7- denitrifications, 2 ' - C- methyladenosines, 2'CmeC, 2 '-C- methylguanosines, 2 '-C- methyluridines, (-)-epigallo catechin Galla Turcica (Galla Helepensis) Acid esters or niclosamide.
5. the use that Menglusitena is used in the medicine treated and/or prevent zika virus infection associated conditions or disease in preparation On the way.
6. the purposes described in claim 5, wherein zika virus infection associated conditions or disease are zika virus infection drawing The microcephaly for rising or Guillain-Barre＆1＆ syndrome.
7. the purposes according to any one of claim 5-6, wherein Menglusitena are combined for preparing with other medicines State medicine.
8. the purposes described in claim 7, wherein the other medicines be the life of Enbrel card, -2 '-C- methyladenosines of 7- denitrifications, 2 ' - C- methyladenosines, 2'CmeC, 2 '-C- methylguanosines, 2 '-C- methyluridines, (-)-epigallo catechin Galla Turcica (Galla Helepensis) Acid esters or niclosamide.
CN201611121927.6A 2016-12-08 2016-12-08 Small molecular drug capable of being used for inhibiting Zika virus infection and application of drug Pending CN106511346A (en)

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WO2018192083A1 (en) * 2017-04-20 2018-10-25 Versitech Limited Zika virus protease inhibitors and methods of use thereof
CN111320670A (en) * 2018-12-14 2020-06-23 复旦大学 Polypeptide for inhibiting Zika virus, dengue virus and yellow fever virus infection and application thereof

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CN112040954A (en) * 2018-04-27 2020-12-04 雷莫内克斯生物制药有限公司 Pharmaceutical composition for preventing or treating flavivirus infection
CN112812028B (en) * 2020-12-31 2022-01-11 中山大学 Anthraquinone compound and application thereof in preparation of anti-Zika or dengue virus drugs

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US6696466B1 (en) * 2000-09-07 2004-02-24 Leslie Joe Dunaway Methods of treating select neuronal inflammatory disorders using hydroxyalkylquinolines
BR112014024287A2 (en) * 2012-03-27 2018-05-08 Duke University compositions and methods for the prevention and treatment of mast cell-induced vascular leakage

Cited By (3)

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Publication number Priority date Publication date Assignee Title
WO2018192083A1 (en) * 2017-04-20 2018-10-25 Versitech Limited Zika virus protease inhibitors and methods of use thereof
US11517581B2 (en) 2017-04-20 2022-12-06 Versitech Limited Zika virus protease inhibitors and methods of use thereof
CN111320670A (en) * 2018-12-14 2020-06-23 复旦大学 Polypeptide for inhibiting Zika virus, dengue virus and yellow fever virus infection and application thereof

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Application publication date: 20170322