Application of macrolides in anti-filovirus infection

A technology of macrolides and filoviruses, which is applied in the field of medicine and can solve the problems that the antiviral effect has not been reported.

Active Publication Date: 2020-02-18
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such as the development of macrolide immunosuppressants (such as tacrolimus, pimecrolimus, sirolimus); the prevention and treatment of cardiovascular diseases [Lip GYH, Beevers DG. Can we treat coronary artery disease with antibiotics Lancet.1997,350(9075):378]; treatment of bullous emphysema [Cheng Shuquan, Ma Xinghe. Research on the clinical application of macrolide antibiotics. Foreign Pharmaceutical Antibiotics Volume. 1999,20(6):253] etc., but its antiviral effect has not been reported

Method used

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  • Application of macrolides in anti-filovirus infection
  • Application of macrolides in anti-filovirus infection
  • Application of macrolides in anti-filovirus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0166] Example 1. Principle of Screening Model

[0167] Filovirus entry into host cells is the first step in virus infection, and inhibiting virus entry can effectively block virus infection. The glycoprotein (Glycoprotein, GP) on the surface of the filamentous virus envelope is a key protein in the process of filamentous entry.

[0168] We synthesized the envelope GP gene of Zaire type Ebola virus (EBOV-Zaire GP, Gene AccessionNo.L11365), Sudan type Ebola virus envelope GP gene (EBOV-Sudan GP, ​​Gene AccessionNo.FJ968794.1 ) and Marburg virus envelope GP gene (Marburg GP, Gene Accession No.NC_001608.3). Expression of GP protein plasmid and pNL4-3-Luc-R by co-transfection - E. - , the EBOV recombinant virus EBV-GP / HIV [Manicassamy B, Wang J, Jiang H, RongL.Comprehensive analysis of ebola virus GP1 in viral entry.J Virol.2005; 79: 4793-805.] and Marburg recombinant virus MGP / HIV [Manicassamy B, Wang J, et al. Characterization of Marburg virus glycoprotein in viral entry. Vi...

Embodiment 2

[0169] Embodiment 2. Experimental method

[0170] In the present invention, EBOV-Zaire (Gene Accession No.L11365), EBOV-Sudan (Gene Accession No.FJ968794.1) and Marburg (Gene Accession No.NC_001608.3) are applied to the anti-filovirus of macrolides Infection for pharmacological activity evaluation:

[0171] Preparation of recombinant virus [Manicassamy B, Wang J, Jiang H, Rong L.Comprehensive analysis of ebola virus GP1 in viral entry.J Virol.2005; 79:4793-805.]: Co-transfect 2μg pcDNA3.1 / EBOV-Zaire GP Plasmid (or 2 μg pcDNA3.1 / EBOV-Sudan GP plasmid or 2 μg pcDNA3.1 / Marburg GP plasmid) and 2 μg pNL4-3-Luc-R - E. - The plasmid was transferred to 293T cells, and the supernatant was collected 48 h after transfection, and the supernatant was filtered through a 0.45 μm filter membrane, and the supernatant contained EBOV-Zaire GP / HIV virus particles (or EBOV-Sudan GP / HIV virus particles or Marburg GP / HIV virus particles), the recombinant virus can be used for infection. Prepare...

Embodiment 3

[0180] Example 3. Cytotoxicity test

[0181] The cytotoxicity of all involved drugs to A549 and 293T cells was determined by MTS method, and the results showed that azithromycin, telithromycin, clarithromycin, carbomycin A, josamycin, beilimycin, midecamycin, mica Oleandomycin, troleandomycin, spiramycin, troleandomycin, tulamycin, fluerythromycin, tilmicosin, rotamycin, erythromycin, amphotericin B, tagram Limus, pimecrolimus, and sirolimus had no cytotoxicity at a final concentration of 10 μM.

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Abstract

The invention discloses an application of a macrolides medicine to preventing inovirus infection. The invention includes an application of the macrolides medicine to prevent or treat inovirus infection. The medicine has a macrolides structural characteristic and is selected from at least one of azithromycin, telithromycin, clarithromycin, carbomycin A, josamycin, kitasamycin, midecamycin, mikamycin, oleandomycin, spiramycin, troleandomycin, tulathromycin, flurithromycin, tilmicosin, rokitamycin, cethromycin, tacrolimus, pimecrolimus, sirolimus, and amphotericin B.

Description

technical field [0001] The invention relates to the application of macrolide drugs in anti-filovirus infection, and belongs to the technical field of medicine. Background technique [0002] Filoviridae, also known as filoviruses, has only one genus of viruses, the genus Filovirus. Filovirus is an enveloped virus with a filamentous appearance and its genome is a single-stranded negative-sense RNA. This genus includes two viruses, namely Ebola virus (EBOV) and Marburg virus (Marburg virus, MBV). ), both of these viruses are controlled viruses, which need to be completed in a biosafety level 4 (P-4) laboratory [Centers for Disease Control and Prevention / National Institutes of Health.Biosafety in Microbiological and Biomedical Laboratories.4th ed.Washington, DC : U.S. Department of Health and Human Services, U.S. Government Printing Office; 1999. DHHS Publication CDC 93-8395.]. Ebola hemorrhagic fever (Ebola hemorrhagic fever, EHF) is caused by Ebola virus, is a serious threat...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/706A61K31/7052A61K31/7048A61K31/436A61P31/14
Inventor 郭颖陈勍霸明宇王丽丽唐克
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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