Application of Isaconazole Salt and Isaconazole in the Preparation of Anti-arenavirus Infection Drugs
A technology of isavuconazole and arenavirus, applied in the field of medicine, can solve problems such as no reports of isavuconazole antiviral activity, and achieve the effects of alleviating the epidemic situation, short treatment period and high fatality rate
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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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