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Application of CNPY3 protein as target for treating dengue fever

A dengue fever target and anti-dengue fever technology, applied in the direction of gene therapy, peptide/protein components, medical preparations containing active ingredients, etc., can solve the problem that there are no vaccines and antiviral drugs to prevent or treat dengue fever, and achieve inhibition of infection, Infection-promoting effect

Pending Publication Date: 2022-07-26
ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the unique pathogenesis of dengue virus infection, there are currently no vaccines and antiviral drugs that can be widely used to prevent or treat dengue fever

Method used

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  • Application of CNPY3 protein as target for treating dengue fever
  • Application of CNPY3 protein as target for treating dengue fever
  • Application of CNPY3 protein as target for treating dengue fever

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1D

[0032] Example 1 Screening of host differential genes during DENV virus infection

[0033] Download the dataset GSE58278 DENV-infected dendritic cells microarray dataset from the GEO public database (https: / / www.ncbi.nlm.nih.gov / geo / query / acc.cgi?acc=GSE58278) using NCBI Online Differences The expression analysis tool GEO2R was used to analyze the differential genes of DENV 2 infected cells and uninfected cells 24 hours after the data set, and screened out the differential genes with p≤0.05 and Log2FC≥1, of which 387 genes were up-regulated and 295 genes were down-regulated.

[0034] In addition, combined with the dengue patient transcriptome dataset GSE51808 (https: / / www.ncbi.nlm.nih.gov / geo / query / acc.cgi), the whole blood of 9 healthy people was used as the control group, and 10 dengue Whole blood of patients with hemorrhagic fever was the infection group, and differential genes with p≤0.05 and Log2FC≥1 were screened out by using the NCBI online differential expression analy...

Embodiment 2

[0036] Example 2CNPY3 expression is inversely correlated with DENV disease severity

[0037] Of these genes analyzed in Example 1, the role of CNPY3 in DENV infection has been poorly studied. Therefore, further studies were carried out using a neonatal mouse DENV-2 infection model.

[0038] DENV-1 (strain name ThD1-0102-01), DENV-2 (strain name New Guinea), DENV-3 (strain name 80-2) and DENV-4 (strain name GD07-) used in the present invention 78) The virus strain was provided by the Center for Disease Control and Prevention of Guangzhou Military Region, China. DENV-1, DENV-2, DENV-3 and DENV-4 were propagated in Vero cells.

[0039]Dengue virus infection in suckling mice experiment: New Guinea DENV 2 was used to intracranially inject 3-day-old Bablc suckling mice (female BALB / c pregnant mice were purchased from the Experimental Animal Center of Army Medical University), and DENV-2 virus was isolated from the brains of suckling mice ( Virus titer 8×10 6 PFU / mL), take 3 μL o...

Embodiment 3

[0048] Example 3CNPY3 plays an important role in Toll-like receptor-dependent immune responses

[0049] Cell and tissue tropism of DENV affects outcomes of DENV infection To investigate the role of CNPY3 in DENV infection, the expression of CNPY3 in healthy human tissues was investigated using the HPA database (https: / / www.proteinatlas.org / ). . The data indicated that CNPY3 RNA and protein were more abundantly expressed in brain, blood, bone marrow and lymphoid tissues ( Figure 4 A). The immune system, liver, and the inner organ system of blood endothelial cells play important roles in the pathogenesis of DHF / DSS. The expression of CNPY3 in various immune cells in blood was further detected using the HPA database.

[0050] Single-cell sequencing data obtained from the HPA database showed that CNPY3 was most highly expressed in dendritic cells, endothelial cells, and monocytes in blood ( Figure 4 B and 4C). Monocytes and dendritic cells (DCs) are the main target cells of...

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Abstract

The invention belongs to the technical field of antiviral drugs, and particularly relates to application of CNPY3 protein as a target spot for treating dengue fever. The invention discloses and identifies an important host protein CNPY3 related to dengue virus infection. The host gene is significantly down-regulated in blood of a dengue patient and in dengue virus infected dendritic cells and THP-1 cells. The expression of the gene is in negative correlation with the dengue disease progress, and is in positive correlation with the expression of most Toll-like receptors. Further research shows that down-regulation of the gene in THP-1 cells inhibits generation of IFN-beta and expression of the ISGs gene and promotes infection of DENV-2. And the expression of the gene is up-regulated in Vero and HEK 293T cells, so that the infection of DENV-2 can be inhibited. The results show that the CNPY3 participates in an innate immune response signal pathway, has an anti-dengue virus effect, and is a potential therapeutic target for dengue fever.

Description

technical field [0001] The invention belongs to the technical field of antiviral drugs, in particular to the use of CNPY3 protein as a target for treating dengue fever. Background technique [0002] Dengue fever is an acute infectious disease caused by Dengue Virus (DV). About 50 to 100 million people are infected with dengue virus every year. Dengue virus infection can cause clinical symptoms ranging from dengue fever (DF) to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DHS). DHF or DHS is characterized by severe hemorrhage and vital organ damage with high mortality, but its pathogenesis is unclear. Due to the unique pathogenesis of dengue virus infection, there are currently no vaccines and antiviral drugs that can be widely used to prevent or treat dengue. Dengvaxia (also known as CYD-TDV), developed by Sanofi Pasteur, is the only vaccine approved for use in about 20 dengue-endemic countries in Asia, Latin America, Oceania and Europe. This vaccine, for peo...

Claims

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Application Information

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IPC IPC(8): C07K14/47C12N15/12A61K38/17A61K48/00A61P31/14
CPCC07K14/47A61K48/005A61P31/14A61K38/00Y02A50/30
Inventor 李晋涛丁晓艳周伃欣何久香周晓杨邱民月
Owner ARMY MEDICAL UNIV