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Application of small-molecule inhibitor in prevention and treatment of respiratory viral pneumonia

A viral pneumonia and inhibitor technology, applied in clinical, biological, and medical fields, can solve problems such as uncontrollable progress and patient death

Active Publication Date: 2021-12-17
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Novel coronavirus pneumonia COVID-19, once it enters the severe stage, its progress will become very difficult to control, and it will easily lead to death of patients
At present, the cause of death of patients caused by SARS-COV-2 infection is not clear

Method used

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  • Application of small-molecule inhibitor in prevention and treatment of respiratory viral pneumonia
  • Application of small-molecule inhibitor in prevention and treatment of respiratory viral pneumonia
  • Application of small-molecule inhibitor in prevention and treatment of respiratory viral pneumonia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1. Kyn significantly induces ACE2 expression through the AHR pathway

[0055] 1. Experimental steps:

[0056] 1. Prepare reagents: Ca-free 2+ / Mg 2+ HBSS+5%FBS+2mM EDTA+collagenase+hyaluronidase, preheated to 37°C; sacrifice the mice, cut the lungs; remove the bronchi and lymph nodes; use Ca-free 2+ / Mg 2+ Wash the contents of the lungs with PBS; cut the lungs into as small pieces as possible, put them into a 50mL centrifuge tube, add 20mL of the reagent prepared in the first step; shake on a horizontal shaker at 37°C and 250rpm for 20min; filter on a 200-mesh filter Transfer the supernatant to a new 50mL centrifuge tube, and add 20mL of the reagent prepared in the first step to the remaining intestinal tissue; shake on a horizontal shaker at 37°C and 250rpm for 20min; filter the supernatant through a 200-mesh filter and transfer it to the previous 50mL centrifuge tube; filtrate After centrifugation at 400 g for 5 min, the obtained cell pellet was lung epith...

Embodiment 2

[0067] Example 2. Interferon β induces ACE2 expression through the IDO-AHR pathway

[0068] 1. Experimental steps

[0069] 1. Prepare reagents: Ca 2+ / Mg 2+ HBSS+5%FBS+2mM EDTA+collagenase+hyaluronidase, preheated to 37°C; sacrifice the mice, cut the lungs; remove the bronchi and lymph nodes; use Ca-free 2+ / Mg 2+ Wash the contents of the lungs with PBS; cut the lungs into as small pieces as possible, put them into a 50mL centrifuge tube, add 20mL of the reagent prepared in the first step; shake on a horizontal shaker at 37°C and 250rpm for 20min; filter on a 200-mesh filter Transfer the supernatant to a new 50mL centrifuge tube, and add 20mL of the reagent prepared in the first step to the remaining intestinal tissue; shake on a horizontal shaker at 37°C and 250rpm for 20min; filter the supernatant through a 200-mesh filter and transfer it to the previous 50mL centrifuge tube; filtrate After centrifugation at 400 g for 5 min, the obtained cell pellet was lung epithelial c...

Embodiment 3

[0074] Example 3. Interferon gamma induces ACE2 expression through the IDO-AHR pathway

[0075] 1. Experimental steps

[0076] 1. The operation of mouse alveolar cell isolation is the same as that described in Example 1 above.

[0077] 2. Divided into the following groups: control group (PBS treatment), interferon gamma group (10ng / ml INF gamma treatment for 48 hours), interferon gamma group plus IDO inhibitor (10ng / ml INF gamma and 0.2mM 1-MT treatment for 48 hours ) and interferon γ group plus AHR inhibitor (10ng / ml INFγ and 4μM CH223191 treated for 48 hours).

[0078] 3. The operations of Western blot detection, BCA protein quantification, gel plate preparation, SDS-PAGE electrophoresis, membrane transfer, antibody incubation, and chemiluminescence imaging were the same as those described in Example 1 above.

[0079] 2. Experimental results

[0080] Western blotting showed that when BAES-2B and mouse type II alveolar epithelial cells were treated with interferon gamma, i...

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Abstract

The invention provides application of a small-molecule inhibitor in prevention and treatment of respiratory viral pneumonia. Specifically, the invention relates to a novel application of an AhR inhibitor in treating or improving virus infection. The inhibitor for treating virus infection provided by the invention can effectively inhibit expression of angiotensin converting enzyme 2 so as to prevent virus from infecting lung tissues, and the AhR inhibitor is expected to become a potential medicine for preventing and treating lung diseases caused by virus infection.

Description

[0001] This application claims priority from patent application 202010552732.7 (priority date June 17, 2020). technical field [0002] This application relates to biological, medical and clinical fields. In particular, it relates to small molecule inhibitors and their use in the prevention and treatment of viral pneumonia. Background technique [0003] The global coronavirus pandemic has had a huge impact on countries around the world. The virus has spread to almost every country in the world in less than 6 months. Some of these countries have already experienced a second wave of outbreaks, while others, such as Russia, Brazil, India and parts of Africa, are still in the first wave. [0004] This new pathogen was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the World Health Organization (WHO) on February 11, 2020. SARS-CoV-2, the cause of coronavirus 2019 (COVID-19), belongs to the same virus family as severe acute respiratory syndrome coronavirus...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/405A61P11/00A61P31/14A61P31/16
CPCA61K45/00A61K31/405A61P11/00A61P31/14A61P31/16
Inventor 黄波刘玉英佟伟民
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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