WO2017124831A1 - Inhibiteur d'infection virale à large spectre - Google Patents

Inhibiteur d'infection virale à large spectre Download PDF

Info

Publication number
WO2017124831A1
WO2017124831A1 PCT/CN2016/107231 CN2016107231W WO2017124831A1 WO 2017124831 A1 WO2017124831 A1 WO 2017124831A1 CN 2016107231 W CN2016107231 W CN 2016107231W WO 2017124831 A1 WO2017124831 A1 WO 2017124831A1
Authority
WO
WIPO (PCT)
Prior art keywords
virus
infection
influenza
adenovirus
coronavirus
Prior art date
Application number
PCT/CN2016/107231
Other languages
English (en)
Chinese (zh)
Inventor
常国辉
罗欢乐
罗保君
罗丽晓
罗彦军
刘京梅
张洁
Original Assignee
中国人民解放军疾病预防控制所
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 中国人民解放军疾病预防控制所 filed Critical 中国人民解放军疾病预防控制所
Publication of WO2017124831A1 publication Critical patent/WO2017124831A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7024—Esters of saccharides
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters

Definitions

  • the present invention belongs to the field of biotechnology and relates to a broad spectrum viral infection inhibitor.
  • Plant compounds are called "seventh type of nutrients" and are widely found in everyday foods. They are a class of non-nutritive chemicals that have a special effect on human health. Related studies have found that some plant compounds have biological activities that inhibit viral infection, and have gradually become one of the hot spots of antiviral research. Preliminary results show that the biological effects of plant compounds are mainly reflected in their effects on the biological properties of cell membranes and changes in the balance of local microenvironment. Some plant compounds change the normality of cell membrane by directly intercalating the lipid bilayer structure of cell membrane. Functional flow and potential difference, which in turn exerts certain biological effects. Problem solution
  • EGCG epigallocatechin gallate
  • E GCG epigallocatechin gallate
  • tannic acid and the astragalus polysaccharide may have a mass ratio of (0.5-1.0) : (0.5-1.0) : (0.5-1.5
  • the preparation for inhibiting viral infection is specifically composed of epigallocatechin gallate (EGCG), tannic acid, and astragalus polysaccharide;
  • EGCG epigallocatechin gallate
  • tannic acid tannic acid
  • astragalus polysaccharide The mass ratio of the tea gallic acid ester (EGCG), the tannic acid and the astragalus polysaccharide is 1: 1: 1.5.
  • the preparation method of the preparation for inhibiting viral infection is also within the scope of protection of the present invention.
  • the preparation method of the preparation for virus infection may specifically include the following steps:
  • the epigallocatechin gallate (EGCG), tannic acid and astragalus polysaccharide are mass ratio (0.5-1.0). : (0.5 - 1.0) : (0.5-1.5) The ratio is mixed to obtain the preparation.
  • the mass ratio of the epigallocatechin gallate (EGCG), the tannic acid, and the xanthine polysaccharide may specifically be 1: 1: 1.5.
  • the preparation for inhibiting viral infection in the preparation of a product for inhibiting viral infection is also within the scope of the present invention.
  • the virus may be four, any three or any two of the following
  • Influenza virus Influenza virus, adenovirus, pox virus and coronavirus.
  • the preparation for inhibiting viral infection in inhibiting viral infection is also within the scope of protection of the present invention.
  • the virus may be four, any three or any two of the following: influenza virus, adenovirus
  • virus-inhibiting infection is specifically as follows (a) or (b):
  • the inhibitory effect of the preparation on the viral infection is embodied as: a mammalian cell as a virus infection target, a virus infected cell homolog or a viral infection
  • the formulation was administered pre-cell, and the half-inhibitory concentration of the formulation against the virus was significantly reduced compared to the positive control drug that inhibited viral infection.
  • the positive control drug is specifically ribavirin (Ribavirin)
  • the mammalian cell (or the host cell described in (b)) when the virus is an influenza virus, the mammalian cell (or the host cell described in (b)) is specifically a canine kidney cell (MDCK cell).
  • the mammalian cell (or the host cell described in (b)) when the virus is an adenovirus, the mammalian cell (or the host cell described in (b)) is specifically a human embryonic kidney cell strain. (293 cells).
  • the mammalian cell (or the host cell described in (b)) when the virus is a poxvirus sputum, the mammalian cell (or the host cell described in (b)) is specifically an African green monkey kidney cell (Vera cell).
  • the mammalian cell (or the host cell described in (b)) when the virus is a coronavirus sputum, the mammalian cell (or the host cell described in (b)) is specifically a mouse fibroblast (17C1-1 cell).
  • the influenza virus is an influenza A virus.
  • the adenovirus is an adenovirus type 5.
  • the poxvirus is a vaccinia virus.
  • the coronavirus is a murine hepatitis coronavirus. More specifically, the influenza A virus is an H1N1 subtype influenza virus. In one embodiment of the present invention, the influenza virus is specifically an H1N1 subtype influenza virus A/Beijing/501/2 009 (H1N1) strain.
  • the adenovirus is specifically 309 strains of adenovirus type 5.
  • the poxvirus is specifically a vaccinia virus WR strain.
  • the coronavirus is specifically a strain of murine hepatitis coronavirus A59.
  • Human embryonic kidney cell line (293 cells), canine kidney cells (MDCK cells), African green monkey kidney cells (Ver o cells) are all ATCC products, and the number of 293 cells is ATCC CRL-1573, the number of MDCK cells.
  • the Vero cell is numbered ATCC CCL-81.
  • Mouse fibroblasts (17C1-1 cells) presented by Professor Stuart Siddell of the University of Bristol, UK, in "Lin Lei, Sun Ying, Wu Xiaoyan, Sun Zounan, Yang Yi, Su Wenli, Hu Yi, Zhu Qingyu, Guo Deyin, Liu Jingmei, Chang Guohui.
  • Adenovirus type 5 (309 strains), described in “Radko S, Jung R, Olanubi 0, Pelka P. Effects of Adenovirus Type 5 El A Isoforms on Viral Replication in
  • Influenza A H1N1 virus (A/Beijing/501/2009 (H1N1) strain
  • Coronavirus murine hepatitis coronavirus A59 strain, abbreviated as MHV-A59
  • MHV-A59 coronavirus A59 strain
  • Culture medium 1), cell growth medium: DMEM medium (Glibo product) as mother liquor, respectively added 10% (volume fraction) fetal bovine serum (Sigma product), 0.2 mg/ml glutamine (Glibo products), lOO U/ml penicillin and streptomycin. 2), the cell maintenance medium, the fetal bovine serum content is 2% (volume fraction), and the rest are the same as 1).
  • Viral proliferation medium The proliferation medium of adenovirus, pox virus and coronavirus is the same as the cell growth medium; the proliferation medium of H1N1 influenza virus needs to be added with 2 g/ml TPCK-Trypsin (Sigma product). The remaining ingredients are the same as the cell growth medium.
  • EGCG Epigallocatechin gallate
  • Tannin Sigma product (analytical purity >99%), part number V900190
  • Astragalus Polysaccharide (APS): Shanghai Jinsui Biotechnology Co., Ltd. (2-(Chloromethyl)-4-(4-ni Trophenyl)-l,3-thiazole) (analytical purity > 70%), product number JS11328; CAS#89250- 26-0.
  • Positive control drug Ribavirin, a product of Meilun Biotechnology. There is currently no standard positive control drug that inhibits viral infection by altering host cell membrane properties. In this study, ribavirin, the most commonly used drug for current antiviral drugs, was used as a control. It was dissolved in PBS buffer before the experiment, and was filtered at 2560 g/ml. After sterilization, it was stored at -20 °C.
  • Multi-functional enzyme instrument American Molecular Devices SpectraMax M5 multi-function microplate reader.
  • MDCK cells, 293 cells, Vero cells and 17C1-1 cells were respectively taken out in liquid nitrogen, and then immersed in a 37 ° C water bath, and then centrifuged at 1000 rpm for 5 min, the supernatant was discarded, and appropriate cell growth medium was added, and the cells were repeatedly blown repeatedly.
  • the cell density was about 2 ⁇ 10 5 /ml, and it was cultured in a cell culture incubator in a T25 cell culture flask at 10 ml/vial. After 24 hours, observe the cells, the adherence of the cells, after 48-72h, or until the cells grow to a density of about 95%, discard the original culture solution, add PBS buffer, rinse twice, 0.5ml
  • 0.25% (0.25g/100ml) EDTA incubated in a 37 ° C incubator, when the cells shrink and become round, quickly add the cell growth medium, stop the digestion, repeat the blow evenly, centrifuge at 1000 rpm, 5 min, discard Clear, the suspension cell concentration is about 1x10 5 /ml, 10ml / bottle, transferred into the T25 cell culture flask, placed in the cell culture incubator, and routinely subcultured.
  • CPE cytopathic method
  • a single cell suspension added to a 96-well microplate, each Hole 200 ⁇ 1, the amount of cells reached 2x10 5 /ml, cultured in a cell culture incubator for 48-72h, until the cell monolayer density is about 80% ⁇ , removed, discarded, and rinsed twice with PBS (MDCK with 2 g /ml TPCK-Trypsin maintain medium rinsing), use virus growth medium to dilute the virus stock solution 10 times to 10 - 3 ⁇ 10 - 13, a concentration of 8 wells per column, 100 ⁇ 1 per well, set up two columns of blank control, The cells were adsorbed for 1 h, the supernatant was discarded, and then the culture medium was added to 200 ⁇ l. Daily microscopic observation, when the virus control group cell lesions were "++++", the experimental results were recorded.
  • the virus titer TCID 5 was calculated according to the Reed-Muench method. .
  • Example 1 Preparation of Plant Extract Compound Formula Virus Infection Inhibitor
  • the epigallocatechin gallate (EGCG), the tannic acid, and the astragalus polysaccharide are uniformly mixed in a mass ratio of 1: 1:1.5 to obtain a plant extract compound formulation.
  • g/ml Diluted by gradient to obtain 2 (Vg/ml, 4 (Vg/ml, 8 (Vg/ml, 16 (Vg/ml, 32 (Vg/ml, 64 (Vg/ml, 128 (Vg/) A total of 6 concentrations of ml. Then different dilutions of the dilution were added to 96-well cell culture plates with 293 cells, MDCK cells, Vero cells and 17C1-1 cells, and the cell density was about 80%. 100 ⁇ 1, 4 duplicate wells were used for each dilution. Normal cells (ie no compound formulation was added) as control. After 2h, the test solution was discarded, and the cells were added to maintain the culture solution.
  • Example 1 The statistical difference between the OD values of each concentration group and the control group (normal cells, that is, without the addition of the composite formulation) was compared by one-way analysis of variance, and the preparation of Example 1 was determined.
  • the maximum non-toxic concentration of the composite formulation ie, the maximum concentration that is not statistically different from the OD value of the control).
  • the inhibitory effect of the composite formulation prepared in Example 1 on various viral infections was determined by the CPE method.
  • the test adenovirus was a 309 strain of adenovirus type 5.
  • a 96-well culture plate containing 293 cells having a monolayer cell growth density of about 80% was taken, the culture solution was drained, and the cells were rinsed with PBS for 3 times, respectively, in three conditions of A, B, and C.
  • the composite formulation prepared in Example 1 was added: [0050] A. Adsorption of the same strain on the virus: an equal volume of 2 x 100 TCID 5 . After mixing the virus solution of the adenovirus type 5 with the double-concentration test substance solution, the mixture solution was added to the cell culture plate, and the mixture was immersed in a cell culture incubator, and after being adsorbed for 1 hour, the virus was discarded. After rinsing the cell surface 3 times with PBS, the cells were added to maintain the culture solution.
  • the virus solution of adenovirus type 5 was 100 ⁇ l in a cell culture incubator, and was discarded after the virus was adsorbed for 1 h. After rinsing the cell surface 3 times with PBS, the cells were added to maintain the culture solution.
  • C After virus adsorption: 100TCID 5 .
  • the virus type 5 of the adenovirus type 5 is ⁇ /well, in a cell culture incubator, and discarded after the virus is adsorbed for 1 hour.
  • test substance is a monomer of three compounds of epigallocatechin gallate (EGCG), tannic acid and xanthine polysaccharide, a composite formulation prepared in Example 1, or a positive control against antiviral infection.
  • Drug ribavirin Concentration of the test solution of a concentration gradient is provided as follows: 2 (Vg / ml, 4 (Vg / ml, 80 ⁇ ⁇ / ⁇ 1, 1 6 (Vg / ml, 32 (Vg / ml, 64 (Vg / ml, 128 (Vg /ml.
  • Each group of experiments was set up with a blank control and a positive control group (the positive control was only 100 TCID 5 was added.
  • the virus, the blank control was only added to the cell maintenance medium), cultured in a cell culture incubator, and observed under an inverted microscope daily.
  • the virus control group ie, the positive control group
  • the half-inhibitory concentration IC 5 was calculated according to the Reed-Muench method. .
  • EGCG tannic acid, astragalus polysaccharide, the plant extract compound formulation prepared in Example 1, and ribavirin were respectively in three ways (A represents a virus adsorption homologous addition inhibitor group, B represents Adding inhibitor group before virus adsorption, C means adding inhibitor group after virus adsorption) Intervention of type 5 adenovirus infection, except for Astragalus polysaccharide can not effectively inhibit adenovirus infection under the conditions of A and C, the other inhibitors are in three Adenovirus infection can be inhibited under all conditions. Among them, EGCG has better effect in inhibiting adenovirus infection under conditions of B and plant extract compound formulation under conditions of A and B.
  • the three plant extracts and their complex formulas can effectively inhibit the infection of type 5 adenovirus by administering one hour before infection.
  • the Astragalus polysaccharide has no effect of inhibiting adenovirus infection after administration of the virus infection and infection.
  • ribavirin can inhibit adenovirus infection, it is administered after infection. The effect was the best, and the half-inhibition concentration was significantly higher before and after infection.
  • EGCG added hydrazine before virus adsorption, which inhibited the virus infection best, and the virus half-inhibition concentration was 162 ⁇ llg/ml. The specific results are shown in Table 2.
  • Table 2 The median inhibitory concentration of each inhibitor against type 5 adenovirus infection (IC 5 .)
  • influenza virus tested was a strain of influenza A H1N1 virus A/Beijing/501/2009 (H1N1) strain.
  • EGCG, tannic acid, astragalus polysaccharide, plant extract compound formulation prepared in Example 1, and ribavirin were respectively in three ways (A represents a virus adsorption homogen addition inhibitor group, B represents Adding inhibitor group before virus adsorption, C means adding inhibitor group after virus adsorption) Intervention of A(H1N1 influenza virus infection), tannic acid under C condition and Astragalus polysaccharide can not effectively inhibit virus infection under three conditions.
  • EGCG, a plant extract complex formulation and ribavirin inhibit viral infection under all three conditions.
  • the compound formulation had the best effect before infection and the same infection, the first half inhibition concentration was only 92 g/ml, and the half inhibition concentration of EGCG, tannic acid and ribavirin was significantly higher than that of the composite formulation. .
  • ribavirin clearly has a greater advantage.
  • tannic acid was added to the virus-adsorbed homologue, which inhibited the virus infection, and the virus half-inhibition concentration was 234 ⁇ 36 g/ml. The specific results are shown in Table 3.
  • test poxvirus is a vaccinia virus WR strain.
  • step one replacing 293 cells with Vero cells, and replacing adenovirus type 5 with
  • the test coronavirus is a murine hepatitis coronavirus A59 strain.
  • step 1 the 293 cells were replaced with 17C1-1 cells, and the adenovirus type 5 was replaced with a coronavirus.
  • EGCG added hydrazine before virus adsorption, which inhibited the virus infection best.
  • the half-inhibition concentration of the virus was 172 ⁇ 14 g/ml.
  • tannic acid and astragalus polysaccharides were added. Can not effectively inhibit the infection of poxvirus.
  • Table 5 The specific results are shown in Table 5.
  • the cytotoxicity of the composite formulation provided by the present invention is not higher than that of the control sample ribavirin which has obtained the safety approval.
  • the prophylactic use of the plant extract compound formulation provided by the present invention at a safe use concentration can effectively inhibit the infection of the type 5 adenovirus, the influenza A H1N1 influenza virus, the poxvirus and the coronavirus. Because the viruses used in the study have different biological characteristics, genetic material and proliferation characteristics, they belong to different virus categories: Type 5 adenovirus is a non-encapsulated DNA virus, and influenza A H1N1 virus is a cystic phased RNA virus.
  • the poxvirus is a cystic DNA virus, and the coronavirus is a single-stranded RNA virus with a capsule. Therefore, the experimental results of the present invention are universal, and the provided compound preparation has further developed into a broad-spectrum virus infection inhibition. The commercial value of the agent.
  • test substance is the composite formula preparation prepared in the first embodiment, the control compound formula preparation 1, the control compound formula preparation 2, the control compound formula preparation 3, or the anti-virus infection positive control drug.
  • Ribavirin the rest of the operation is the same as step one of the third embodiment.
  • the comparative compound formula preparation 1, the control compound formula preparation 2 and the control compound formula preparation 3 are formulated as follows:
  • Control compound formulation 1 The epigallocatechin gallate, tannic acid and xanthine polysaccharide were mixed at a mass ratio of 0.5: 1:0.5.
  • Control compound formulation 2 The epigallocatechin gallate, tannic acid and astragalus polysaccharide were mixed in a ratio of 1:0.5:1 by mass ratio.
  • Control compound formulation 3 The epigallocatechin gallate, tannic acid and astragalus polysaccharide were mixed at a mass ratio of 1: 1:1.
  • Table 6 The half-inhibitory concentration of different composite formulations on infection with type 5 adenovirus (IC 5 .)
  • test substance is the composite formula preparation prepared in the first embodiment, the control compound formula preparation 1, the control compound formula preparation 2, the control compound formula preparation 3, or the anti-viral infection positive control drug.
  • Ribavirin the rest of the operation is the same as step 2 of the third embodiment.
  • the comparative compound formula preparation 1, the control compound formula preparation 2 and the control compound formula preparation 3 are formulated as follows:
  • Control compound formulation 1 The epigallocatechin gallate, tannic acid and astragalus polysaccharide were mixed in a ratio of 0.5: 1:0.5.
  • Control compound formulation 2 The epigallocatechin gallate, tannic acid and astragalus polysaccharide were mixed according to a mass ratio of 1:0.5:1.
  • Comparative Compound Formulation Formulation 3 The epigallocatechin gallate, tannic acid, and xanthine polysaccharide were mixed at a mass ratio of 1:1:1. [0091] The results showed that the half-inhibitory concentration (IC 5 ) of the control compound formulation 1, the control compound formulation 2 and the control compound formulation 3 against the influenza A H1N1 influenza virus infection was significant under the conditions of B, C and C. The composite formulation prepared in Example 1 was lower (p ⁇ 0.05). See Table 7 for the specific results.
  • the test substance is the composite formula preparation prepared in the first embodiment, the control compound formula preparation 1, the control compound formula preparation 2, the control compound formula preparation 3, or the anti-viral infection positive control drug.
  • Ribavirin the rest of the operation is the same as the third step of the third embodiment.
  • the comparative compound formula preparation 1, the control compound formula preparation 2 and the control compound formula preparation 3 are formulated as follows:
  • Control compound formulation 1 The epigallocatechin gallate, tannic acid and astragalus polysaccharide were mixed in a ratio of 0.5: 1:0.5.
  • Control compound formulation 2 The epigallocatechin gallate, tannic acid and astragalus polysaccharide were mixed according to a mass ratio of 1:0.5:1.
  • Control compound formulation 3 The epigallocatechin gallate, tannic acid and astragalus polysaccharide were mixed according to a mass ratio of 1: 1:1.
  • test substance is the composite formula preparation prepared in the first embodiment, the control compound formula preparation 1, the control compound formula preparation 2, the control compound formula preparation 3, or the anti-viral infection positive control drug.
  • Ribavirin the rest of the operation is the same as step 4 of Example 3.
  • the comparative compound formula preparation 1, the control compound formula preparation 2 and the control compound formula preparation 3 are formulated as follows:
  • Comparative compound formulation 1 The epigallocatechin gallate, tannic acid, and xanthine polysaccharide were mixed at a mass ratio of 0.5:1:0.5.
  • Control compound formulation 2 The epigallocatechin gallate, tannic acid and xanthine polysaccharide were mixed in a ratio of 1:0.5:1 by mass ratio.
  • Control compound formulation 3 The epigallocatechin gallate, tannic acid and astragalus polysaccharide were mixed in a ratio of 1:1:1.
  • Coronavirus (mouse hepatitis)
  • Virus, MHV), poxvirus, adenovirus type 5 (Ad-5) and influenza A (H1N1) virus were used as experimental subjects.
  • the method of observing cytopathic lesions was used to analyze epigallocatechin catechins under different infection conditions.
  • the three plant compound monomers and their mixed preparations of acid ester (EGCG), tannic acid and astragalus polysaccharides inhibit the regularity and characteristics of viral infection.
  • Prophylactic use of plant compound monomers such as EGCG and tannic acid and a mixture of plant extracts at a safe use concentration can effectively inhibit type 5 adenovirus, alpha H1N1, 3 ⁇ 4? susceptible virus, poxvirus and coronal Virus infection.
  • the viruses used in the study have different biological characteristics, genetic material and proliferation characteristics, and belong to different virus categories: Type 5 adenovirus is a non-encapsulated DNA virus, and type A H1N1 influenza virus is a cystic phased RNA virus.
  • the poxvirus is a cystic DNA virus, and the coronavirus is a single-stranded RNA virus with a capsule. Therefore, the experimental results are universal, and the related plant compound monomers and compound formula mixtures have been further developed into broad-spectrum virus infection inhibitors.
  • Business value

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Un inhibiteur d'infection virale à large spectre est formé par mélange de gallate d'épigallocatéchine, d'acide tannique et d'un polysaccharide d'astragale. Le rapport pondéral entre le gallate d'épigallocatéchine, l'acide tannique et le polysaccharide d'astragale est le suivant : (0,5-1,0)/(0,5-1,0)/(0,5-1,5). Cette préparation est capable d'inhiber efficaclement les infections à adénovirus 5, les infections par le virus de la grippe A (H1N1), les infections à poxvirus et les infections à coronavirus.
PCT/CN2016/107231 2016-01-18 2016-11-25 Inhibiteur d'infection virale à large spectre WO2017124831A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201610030808.3 2016-01-18
CN201610030808 2016-01-18

Publications (1)

Publication Number Publication Date
WO2017124831A1 true WO2017124831A1 (fr) 2017-07-27

Family

ID=59361416

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2016/107231 WO2017124831A1 (fr) 2016-01-18 2016-11-25 Inhibiteur d'infection virale à large spectre

Country Status (1)

Country Link
WO (1) WO2017124831A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113209112A (zh) * 2021-02-06 2021-08-06 广州市朝利良生物科技有限公司 基于ace2与s蛋白结合靶点的抗新型冠状病毒药物及其应用
WO2024022411A1 (fr) * 2022-07-26 2024-02-01 Syneurx International (Taiwan) Corp. Composés et compositions pour le traitement de la grippe

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105535012A (zh) * 2016-01-27 2016-05-04 中国人民解放军疾病预防控制所 一种广谱性病毒感染抑制剂
CN105560268A (zh) * 2016-01-27 2016-05-11 中国人民解放军疾病预防控制所 一种用于抑制流感病毒感染的制剂
CN105560351A (zh) * 2016-01-27 2016-05-11 中国人民解放军疾病预防控制所 一种用于抑制腺病毒感染的制剂
CN105663218A (zh) * 2016-01-27 2016-06-15 中国人民解放军疾病预防控制所 一种用于抑制痘病毒感染的制剂
CN105687226A (zh) * 2016-01-27 2016-06-22 中国人民解放军疾病预防控制所 一种用于抑制冠状病毒感染的制剂

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105535012A (zh) * 2016-01-27 2016-05-04 中国人民解放军疾病预防控制所 一种广谱性病毒感染抑制剂
CN105560268A (zh) * 2016-01-27 2016-05-11 中国人民解放军疾病预防控制所 一种用于抑制流感病毒感染的制剂
CN105560351A (zh) * 2016-01-27 2016-05-11 中国人民解放军疾病预防控制所 一种用于抑制腺病毒感染的制剂
CN105663218A (zh) * 2016-01-27 2016-06-15 中国人民解放军疾病预防控制所 一种用于抑制痘病毒感染的制剂
CN105687226A (zh) * 2016-01-27 2016-06-22 中国人民解放军疾病预防控制所 一种用于抑制冠状病毒感染的制剂

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
JING-YAO PANG ET AL.: "Green tea polyphenol, epigallocatechin-3-gallate, possesses the antiviral activity necessary to fight against the hepatitis B virus replication in vitro", JOURNAL OF ZHEJIANG UNIVERSITY- SCIENCE B(BIOMEDICINE & BIOTECHNOLOGY, vol. 15, no. 6, 30 June 2014 (2014-06-30), pages 533 - 539, XP036279641, ISSN: 1673-1581 *
LI, LIYA ET AL.: "Experimental Study on the Anti-influenza Effect of Astragalus Polysaccharide", CHINESE JOURNAL OF TRADITIONAL MEDICAL SCIENCE AND TECHNOLOGY, vol. 9, no. 6, 31 December 2002 (2002-12-31), pages 354 and 355, ISSN: 1005-7072 *
LIU, XUAN ET AL.: "Inhibitory Effect of Tannic Acid on Vaccinia Virus in Vitro", LETTERS IN BIOTECHNOLOGY, vol. 26, no. 6, 30 November 2015 (2015-11-30), ISSN: 1009-0002 *
YANG, YI ET AL.: "Effect of Plant Polyphenols on the Membrane Fluidity of 293a Cells Infected by Adenovirus-5", PROGRESS IN MODERN BIOMEDICINE, vol. 15, no. 18, 30 June 2015 (2015-06-30), ISSN: 1673-6273 *
ZHANG, XIBEN ET AL.: "A Survey of Application Research on Antiviral Effects of Astragalus Polysaccharide", GUIZHOU ANIMAL SCIENCE AND VETERINARY MEDICINE, vol. 33, no. 1, 31 March 2009 (2009-03-31), pages 22 and 23, ISSN: 1007-1474 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113209112A (zh) * 2021-02-06 2021-08-06 广州市朝利良生物科技有限公司 基于ace2与s蛋白结合靶点的抗新型冠状病毒药物及其应用
CN113209112B (zh) * 2021-02-06 2021-12-24 广州市朝利良生物科技有限公司 基于ace2与s蛋白结合靶点的抗新型冠状病毒药物及其应用
WO2024022411A1 (fr) * 2022-07-26 2024-02-01 Syneurx International (Taiwan) Corp. Composés et compositions pour le traitement de la grippe

Similar Documents

Publication Publication Date Title
CN105687226B (zh) 一种用于抑制冠状病毒感染的制剂
Hakobyan et al. Apigenin inhibits African swine fever virus infection in vitro
Milewska et al. Novel polymeric inhibitors of HCoV-NL63
Chiow et al. Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection
Ishag et al. Griffithsin inhibits Japanese encephalitis virus infection in vitro and in vivo
Sobrinho et al. Antiviral activity on the Zika virus and larvicidal activity on the Aedes spp. of Lippia alba essential oil and β-caryophyllene
Makau et al. Anti-influenza activity of Alchemilla mollis extract: Possible virucidal activity against influenza virus particles
CN105535012B (zh) 一种广谱性病毒感染抑制剂
Hosseini et al. Anti-influenza activity of a novel polyoxometalate derivative (POM-4960)
Chen et al. Magnolol protects Ctenopharyngodon idella kidney cells from apoptosis induced by grass carp reovirus
CN113304200B (zh) 五味子提取物的新应用
WO2017124831A1 (fr) Inhibiteur d'infection virale à large spectre
US20100278943A1 (en) Anti viral composition
CN113288907B (zh) 环烯醚萜化合物在制备抗冠状病毒药物中的应用
Gao et al. Fucosylated oligosaccharide Lacto-N-fucopentaose I ameliorates enterovirus 71 infection by inhibiting apoptosis
Zheng et al. In vitro screening of traditional Chinese medicines compounds derived with anti-encephalomyocarditis virus activities
Abd et al. Antiviral activity of limonin against Newcastle disease virus in vitro
da Silva Rodrigues et al. Synthesis and virucide activity on zika virus of 1, 2, 3-triazole-containing vanillin derivatives
CN105560351B (zh) 一种用于抑制腺病毒感染的制剂
EP4125938B1 (fr) Utilisation de dérivés de polystyrène sulfoné dans le traitement et/ou la prophylaxie d'une infection provoquée par le virus zika
CN108354923A (zh) 二氢杨梅素在制备抗流感病毒药物中的应用
KR20090125879A (ko) 항ｈｉｖ제 조성물
CN105560268B (zh) 一种用于抑制流感病毒感染的制剂
CN105663218B (zh) 一种用于抑制痘病毒感染的制剂
Obłoza et al. Polymers as candidates for broad‐spectrum antivirals—in vitro inhibition of Z ika virus with sodium polyanethole sulfonate

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16886091

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16886091

Country of ref document: EP

Kind code of ref document: A1