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Application of enc002 and its analogs in the treatment or prevention of enterovirus infection

A technology for enterovirus and hand, foot and mouth disease virus, which can be applied in antiviral agents, medical preparations containing active ingredients, and drug combinations, etc., and can solve problems such as increasing the complexity and difficulty of hand, foot and mouth disease.

Active Publication Date: 2022-06-28
CHINA INSPECTION SCI PHARM BEIJING GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the same time, there is a new epidemic trend of hand, foot and mouth disease in China. For example, the epidemiological survey from 2012 to 2016 showed that CV-A16 and other enteroviruses in Shandong Province replaced EV71 as the main pathogens of hand, foot and mouth disease in this area; many provinces in China The city reports that the prevalence of CV-A6 has increased in recent years and has become the main epidemic pathogen of hand, foot and mouth disease. Hand, foot and mouth disease presents a variety of enteroviruses alternating or co-circulating, which increases the complexity and difficulty of controlling hand, foot and mouth disease

Method used

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  • Application of enc002 and its analogs in the treatment or prevention of enterovirus infection
  • Application of enc002 and its analogs in the treatment or prevention of enterovirus infection
  • Application of enc002 and its analogs in the treatment or prevention of enterovirus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1. Screening of small molecule compounds with anti-enterovirus activity

[0066] Based on structural biology combined with supercomputer analysis, a new target 3A protein was selected to screen small molecule compounds in the marketed drug library (Aprroved), natural product library and InterBioScreen library. The virtual screening strategy refers to the screening method described in the literature "Computational protein–ligand docking and virtual drug screening with the AutoDock suite. Nature Protocols, 2016". The amino acid sequence of the 3A protein is as follows: GPPKFRPIRISLEEKPAPDAISDLLASVDSEEVRQYCREQGWIIPETPTNVERHLNRAVLVMQSIATVVAVVSLVYVIYKLFAGFQ. The compound ENC002 (compound number in this laboratory) was screened, its CAS number is 849018-64-0, and its molecular formula is C 23 H 18 ON 4 , the structure is as figure 1 shown.

Embodiment 2

[0067] Example 2. Pharmacodynamic detection of compound ENC002 on human enterovirus

[0068] 1. Cell culture, amplification and purification of EV-A71 virus

[0069] RD cells were cultured in DMEM medium containing 10% FBS. When the number of cells is sufficient, they are divided into 10 cm dishes at a density of 70%. Incubate in a 37°C carbon dioxide incubator. 24 hours later, EV-A71 virus was diluted with DMEM medium, the medium in the cell culture dish was discarded, 4 ml of virus dilution was added to each dish of cells, and EV-A71 virus was inoculated at MOI=1. After adsorption at 37°C for 1 hour, the supernatant was discarded, and 10 ml of DMEM medium containing 5% FBS was added. Incubate at 37°C for 48 hours, and observe whether the cells reach 50% shedding. The supernatant was collected and centrifuged at 2000 rpm for 10 minutes. Take the supernatant. 5×PEG8000 NaCl solution was prepared and sterilized by autoclaving at 121°C for 30 minutes. After cooling at room...

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Abstract

The present invention relates to the application of small molecule compounds in virus treatment, in particular to the application of ENC002 and its analogues in the treatment or prevention of enterovirus infection. Provided is the use of the compound of formula (a) in the preparation of a medicament for inhibiting enterovirus replication. One or more hydrogen atoms on any aromatic ring of formula (a) are replaced by R 1 replace, R 1 for C 1‑6 Alkyl, 3‑7 membered ring, nitro, halogen, alkoxy, amino, sulfonate, aryl, heterocyclyl, hydroxyl, carboxyl, trifluoromethyl, nitrile, ‑C(O)‑O -C 1‑6 Alkyl or N‑C 1‑6 Alkyl; A is O, N, S or C; R 2 for hydrogen, C 1‑6 Alkyl, 3‑7 membered ring, aryl, heterocyclyl, trifluoromethyl or amino; R 3 for hydrogen, C 1‑6 Alkyl, 3-7 membered ring, aryl, heterocyclyl, trifluoromethyl or amino. The compound can well inhibit enterovirus, and has great application prospects in the development of anti-enterovirus drugs.

Description

technical field [0001] The present invention relates to the application of small molecule compounds in virus treatment, in particular to the application of ENC002 and its analogs or derivatives in the treatment or prevention of enterovirus infection. Background technique [0002] Enteroviruses belong to the Picornaviridae family, which includes a variety of human and animal viruses, including nine groups of enteroviruses A-J, three groups of rhinoviruses, and types A-D of enteroviruses are human enteroviruses. Enterovirus A71 (Enterovirus-A71, EV-A71), Coxsackievirus B3 (Coxsackievirus B3, CVB3), Coxsackievirus A16 (Coxsackievirus A16, CVA16), poliovirus ( Poliovirus, PV) and other viruses are important human pathogenic viruses [1]. Symptoms and complications caused by different enterovirus infections vary widely. The main symptoms are atypical fever, central nervous system diseases (such as aseptic meningitis, encephalitis, non-polio paralysis), myocarditis, pericarditis,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/527A61P31/14A61P25/00A61P9/00A61P11/00
CPCA61K31/527A61P31/14A61P25/00A61P9/00A61P11/00Y02A50/30
Inventor 朱水芳丛浩龙王晨光田志清姜帆
Owner CHINA INSPECTION SCI PHARM BEIJING GRP CO LTD