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Application of melatonin in preparation of medicine for inhibiting expression of novel coronavirus SARS-CoV-2 receptor

A coronavirus, sars-cov-2 technology, applied in the medical application field of airway inflammation, to achieve the effect of broadening the types of drugs and reducing allergic airway inflammation

Pending Publication Date: 2022-05-06
THE FIRST AFFILIATED HOSPITAL OF ANHUI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

No studies have reported the role of melatonin in inhibiting the expression of key receptors for SARS-CoV2

Method used

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  • Application of melatonin in preparation of medicine for inhibiting expression of novel coronavirus SARS-CoV-2 receptor
  • Application of melatonin in preparation of medicine for inhibiting expression of novel coronavirus SARS-CoV-2 receptor
  • Application of melatonin in preparation of medicine for inhibiting expression of novel coronavirus SARS-CoV-2 receptor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: A mouse model of allergic airway inflammation was constructed to detect the regulatory effect of melatonin on allergic airway inflammatory diseases.

[0023] The model of allergic airway inflammation was constructed by using female C57BL / 6 mice aged 6-8 weeks, sensitized on the 0th day and the 7th day, and given intraperitoneal injection of 500 μl ovalbumin (Ovalbumin, OVA) suspension (containing 10 μg OVA and 1 mg potassium aluminum sulfate). The challenge began on the 14th day, and the mice in the model group were given 1% OVA nebulization for 30 minutes, and the nebulization continued for 7 days. Mice in the melatonin intervention group were intraperitoneally injected with 30 mg / kg melatonin 1 hour before each challenge. Tested 24 hours after the last nebulization, if figure 1 Shown in A. After the blood was taken from the mice in each group, the right lung was ligated, and the left lung was lavaged five times with pre-cooled phosphate buffered saline s...

Embodiment 2

[0027] Example 2: In a mouse model of allergic airway inflammation, melatonin can effectively inhibit the expression of OVA-induced SARS-CoV-2-related receptors (ACE2, TMPRSS2, Calmodulin and ADAM17).

[0028]SARS-CoV-2 relies on two key proteins, ACE2 and TMPRSS2, for efficient entry into host cells. The ectodomain of ACE2 can be cleaved into a soluble form by ADAM17, thereby facilitating the entry of SARS-CoV into cells through endocytosis. On the contrary, Calmodulin can inhibit the shedding of ACE2 ectodomain, thereby retaining ACE2 in the cell membrane, and membrane-bound ACE2 can promote SARS-CoV to enter cells through fusion.

[0029] according to figure 1 A mouse model of allergic airway inflammation was constructed, and melatonin was given to intervene. The expression of SARS-CoV-2 receptors ACE2, TMPRSS2, Calmodulin and ADAM17 in mouse lung tissue was detected by western blot. The results showed that OVA stimulation significantly increased the protein expression o...

Embodiment 3

[0032] Example 3: Melatonin significantly inhibited the expression of inflammatory factors in human primary bronchial epithelial cells (HBECs) after OVA stimulation.

[0033] To examine the regulatory effect of melatonin on OVA-induced inflammation in human bronchial epithelial cells, primary human bronchial epithelial cells (HBECs), which are the main target cells of SARS-CoV-2, were isolated and cultured in this example. The cells were obtained from lung cancer patients undergoing lobectomy, and bronchial epithelial cells were isolated from the airway tissue >3cm from the edge of the tumor tissue, and cultured at 37°C with 5% CO 2 condition.

[0034] The identification of primary human bronchial epithelial cells was labeled with cytokeratin CK17 / 19 by immunofluorescence, and the cells in the logarithmic growth phase were taken to prepare cell slides, which were fixed, permeabilized, and blocked, then incubated with CK17 / 19 antibodies, and passed overnight at 4°C , immunoflu...

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Abstract

The invention belongs to the field of airway inflammation medicine application, and relates to application of melatonin in preparation of a medicine for inhibiting expression of a novel coronavirus SARS-CoV-2 receptor. In the application, the melatonin can effectively alleviate OVA-induced allergic airway inflammation, and can significantly inhibit expression increase of a plurality of SARS-CoV-2 related key receptors, including ACE2, exfoliated sACE2, TMPRSS2, Calmodulin and ADAM17, in mouse and human primary bronchial epithelial cells caused by respiratory allergen exposure, so that the melatonin can be used for inhibiting the expression increase of a plurality of SARS-CoV-2 related key receptors, such as ACE2, exfoliated sACE2, TMPRSS2, Calmodulin and ADAM17. It is indicated that airway inflammatory diseases such as asthma may be a risk factor of SARS-CoV-2 infection, and the melatonin significantly inhibits expression of an SARS-CoV-2 receptor, especially ACE2 and shedding of an extracellular domain, so that a basis is provided for application of the melatonin in preparation of drugs for treating novel coronavirus pneumonia (COVID-19).

Description

technical field [0001] The present invention relates to the field of medical application of airway inflammation, relates to the new use of substances, in particular to the application of melatonin in the preparation of drugs for inhibiting the expression of novel coronavirus SARS-CoV-2 receptors. Background technique [0002] The novel coronavirus pneumonia (COVID-19), caused by the novel coronavirus SARS-CoV-2, has rapidly spread to all parts of the world and led to a large-scale epidemic worldwide. To date, numerous studies have analyzed comorbidities and risk factors in patients with COVID-19. Among them, asthma, which is characterized by chronic airway inflammation, can impair the immune system and therefore may be at higher risk of infection with SARS-CoV-2. Therefore, protection against chronic lung diseases such as severe asthma and COPD (chronic obstructive pulmonary disease) is advocated to reduce the risk of infection with SARS-CoV-2. [0003] SARS-CoV-2 relies o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4045A61P31/14A61P11/00A61P37/08
CPCA61K31/4045A61K9/0053A61P31/14A61P11/00A61P37/08
Inventor 吴惠梅费广鹤谢邱梦赵翠翠韦媛媛章海云
Owner THE FIRST AFFILIATED HOSPITAL OF ANHUI MEDICAL UNIV
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