Isavuconazole and application thereof to preparation of medicine for resisting to arenavirus infection

A technology of essaconazole and arenavirus, which is applied in the field of medicine and can solve the problems such as no reports of essaconazole antiviral activity

Active Publication Date: 2019-05-14
INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is no report on the antiviral activity of Isaconazole and its prodrug Isaconazolium sulfate, including anti-arenavirus activity, after searching the literature

Method used

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  • Isavuconazole and application thereof to preparation of medicine for resisting to arenavirus infection
  • Isavuconazole and application thereof to preparation of medicine for resisting to arenavirus infection
  • Isavuconazole and application thereof to preparation of medicine for resisting to arenavirus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1. Evolutionary relationship of arenaviruses

[0047] Arenaviruses infecting mammals are divided into Old World arenaviruses and New World arenaviruses according to their geographical distribution. There are 12 types of Old World arenaviruses, including lymphocytic choriomeningitis virus, Lassa virus, Ruyo virus, Luna virus, Mobala virus, Gairo virus, Mariental virus, Mopeia virus, Wenzhou virus, Ippy virus, MerinoWalk virus, Okahandja virus and Lunk virus. There are 18 species of arenaviruses in the New World, subdivided into 4 clades (Clades), clade A (Clade A) includes Flexal virus, Allpahuayo virus, Pirital virus, Parana virus and Pichinde virus; / rec) includes Bear Canyon virus, Tamiami virus, and whitewater Arroyo virus; clade B (Clade B) includes Amapari virus, Guanarito virus, Cupixi virus, Chapare virus, Sabia virus, Tacaribe virus, Junin virus and Machupo virus; clade C (Clade C) includes Latino virus and Oliveros virus. Taking the NCBI reference st...

Embodiment 2

[0048] Example 2. Principles of Screening Models

[0049] The entry of arenaviruses into host cells is the first step in virus infection, and inhibiting the entry of viruses can effectively block virus infection. The glycoprotein (Glycoprotein, GP) on the surface of the arenavirus envelope is a key protein in the entry process of arenaviruses.

[0050] Genes that will express arenavirus envelope GP: Lassa virus-Josiah strain GP (LASV-Josiah GP, gene accession number NC_004296), lymphatic choriomeningitis virus-Armstrong53b strain GP (LCMV-Arm53b GP, gene accession number AY847350), Lujo virus GP (LUJV GP, gene accession number FJ952384), Machupo virus-Carvallo strain GP (MACV-Carvallo GP, gene accession number NC_005078), Guanarido virus-S56764 strain GP (GTOV-S56764GP , gene accession number AY572554), Junin virus-XJ13 strain GP (JUNV-XJ13GP, gene accession number FJ805378), Sabia virus-SPH114202 strain (SABV-SPH114202GP, gene accession number NC_006317), whitewater Arroyo v...

Embodiment 3

[0051] Embodiment 3. Experimental method and result

[0052] LASV-Josiah, LCMV-Arm53b, LUJV, MACV-Carvallo, GTOV-S56764, JUNV-XJ13, SABV-SPH114202, WWAV-9310141 and CHPV-810419 were used in the present invention Evaluation of pharmacological activity of conazole against arenavirus infection:

[0053] Recombinant virus preparation [Wang J, Rong L et.al.A Comparative High-Throughput Screening Protocol to Identify Entry Inhibitors of Enveloped Viruses.J BiomolScreen.2014; 19(1):100–107.]: co-transfection of pCMV / LASV- Josiah GP plasmid (or pCMV / LCMV-Arm53bGP plasmid or pCMV / LUJV GP plasmid or pcDNA3.1+ / MACV-Carvallo GP plasmid or pCMV / GTOV-S56764GP plasmid or pCMV / JUNV-XJ13GP plasmid or pCMV / SABV-SPH114202GP plasmid or pCMV / WWAV-9310141GP plasmid or pCMV / CHPV-810419GP plasmid) and pNL4-3-Luc-R - E. - Put the plasmid into 293T cells, collect the supernatant 48 hours after transfection, and filter the supernatant through a 0.45 μm filter membrane. The supernatant contains arena ...

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Abstract

The invention discloses isavuconazole and application thereof (BAL 4815) to preparation of medicine for resisting to arenavirus infection and combined application of isavuconazole and other medicine for resisting viruses.

Description

technical field [0001] The invention relates to the application of Isavuconazonium salt (Isavuconazonium) and Isavuconazole (Isavuconazole; BAL4815) in anti-arenavirus infection, and belongs to the technical field of medicine. The present invention includes the single or combined use of the isaconazole salt and the issaconazole in the prevention or treatment of anti-arenavirus. Background technique [0002] Arenaviruses are a class of enveloped negative-strand RNA viruses. According to the latest updated virus taxonomy standards ["ViralTaxonomy:2015 Release". ICTV.International Committee on Taxonomy of Viruses. Retrieved 15 December 2016], Arenaviridae ( Arenaviridae) currently includes two genera, Mammarenavirus infecting mammals and Reptarenavirus infecting snakes, among which arenaviruses infecting mammals are divided into Old World arenaviruses according to their geographical distribution (Old World Arenavirus, OW), such as Lassa virus (LASV), Mopeia virus (Mopeia virus...

Claims

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Application Information

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IPC IPC(8): A61K31/4439A61K31/427A61P31/14
Inventor郭颖张晓雨唐克陈勍
OwnerINST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI