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Composition for treating enterovirus infection and drug combination method

A technology of enterovirus and composition, applied in the field of biomedicine

Active Publication Date: 2016-06-15
INST PASTEUR OF SHANGHAI CHINESE ACADEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To date there is no effective drug treatment for enterovirus infection and available treatment options are limited to supportive care, intravenous immunoglobulin, or ribavirin [5， 7] , so it is imminent to find antiviral drugs

Method used

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  • Composition for treating enterovirus infection and drug combination method
  • Composition for treating enterovirus infection and drug combination method
  • Composition for treating enterovirus infection and drug combination method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0136] Embodiment 1 single-component activity assay

[0137] Itraconazole, rupintravir, favipiravir, suramin and GW5074 can effectively inhibit the infection of cells by EV71 in a dose-dependent manner.

[0138] Figure 1. Itraconazole, rupinetravir, favipiravir, suramin and GW5074 inhibit the infection of EV71. (A) 2-fold dilutions of itraconazole, rufentravir, favipiravir, suramin and GW5074 were added to RD cells, and the cell viability was detected by CellTiter-Glo kit after adding virus or culture medium for 96 hours , to detect the inhibitory effect of four compounds on EV71 and their cytotoxicity. (B) Add virus and 2-fold dilutions of itraconazole, rupintravir, favipiravir, suramin and GW5074 to RD cells, collect supernatant after 48 hours of culture, and use TCID 50 method to determine the virus titer. Results were processed using GraphpadPrism5. The data in the figure are from two independent parallel experiments, and the error bars represent the standard deviation...

Embodiment 2

[0139] Example 2 Favipiravir acts on enterovirus 71 type 3D protein

[0140] By screening viruses resistant to favipiravir, the inventors obtained two strains of resistant viruses. The virus titer reduction experiment showed that both strains of the virus could produce drug resistance to favipiravir, and through sequence analysis, the inventors found that the same mutation appeared on the 3D protein. Drug-resistant virus phenotype experiments proved that EV71 with a mutation at position 121 of the 3D protein was resistant to favipiravir. Using the reverse genetics system, the inventors constructed a virus with the mutation, and verified its drug resistance to Favipiravir. The results showed that mutation of the 121st position of the 3D protein of enterovirus 71 from serine to aspartic acid would confer drug resistance to EV71, so the inventors concluded that Favipiravir acts on the 3D protein of EV71. In addition, the inventors tested the inhibitory effects of itraconazole, ...

Embodiment 3

[0142] Embodiment 3 combined activity test

[0143] The combination of itraconazole, rupintravir, favipiravir, suramin and GW5074 produced synergistic, additive or antagonistic effects in the treatment of EV71 infection. The result is as image 3 shown.

[0144] image 3 . The interaction effect of different drug combinations in the treatment of EV71 infection. The 3D graph was made using MacSynergy II software, and the data in the graph came from at least three independent parallel experiments. (A) combination of itraconazole and GW5074, (B) combination of itraconazole and suramin, (C) combination of suramin and rupinetravir, (D) combination of favipiravir and rupinetravir, (E ) combination of favipiravir and suramin, (F) combination of favipiravir and itraconazole. The horizontal plane represents the interaction of the two drugs as an additive effect, the point above the horizontal plane represents the effect of the two drugs as a synergistic effect, and the points belo...

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Abstract

The invention provides composition for treating enterovirus infection and a drug combination method and particularly provides composition for inhibiting enteroviruses. The composition comprises a first active ingredient and a second active ingredient, wherein the first active ingredient is a 3D protein inhibitor of enterovirueses such as EV71, and the second active ingredient is a capsid protein inhibitor of enteroviruses such as EV71. Experimental results show that the pharmaceutical composition has a remarkable synergistic function, and cytotoxicity of the composition in detected combination concentration is not enhanced.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular, the invention relates to a composition for treating enterovirus infection and a combined drug method. Background technique [0002] Enteroviruses are picornaviridae viruses with single-stranded positive-sense RNA, and more than 100 serotypes have been found so far. Most enteroviral infections cause no severe symptoms or only mild illness, but often have serious consequences in children and immunocompromised people [1] . Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) in the Enterovirus genus are the main pathogens causing hand-foot-mouth disease in infants and young children in the Asia-Pacific region [2] . Symptoms of hand, foot and mouth disease are usually mild, such as fever, sore throat, diarrhea, local rash, etc., but some patients will develop central nervous system (CNS) diseases, such as aseptic meningitis, fatal encephalitis and even death [3-5] . EV71 is the main...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/4965A61K31/185A61P31/14C12N7/00G01N33/50C12R1/93
CPCA61K31/185A61K31/4965A61K45/06C12N7/00C12N2770/32321G01N33/5008A61K2300/00
Inventor 邹罡艾德铭王一卓
Owner INST PASTEUR OF SHANGHAI CHINESE ACADEMY OF SCI
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