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Application of ellipticine hydrochloride in preparation of anti-streptococcus suis hemolysin drug

A technology of ellipticine and Streptococcus suis, which is applied in the field of microbial infectious diseases and medicine, can solve problems such as inability to alleviate the impact, and achieve the effect of reducing damage

Active Publication Date: 2021-01-29
HUAZHONG AGRI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although commonly used antibiotics can kill Streptococcus suis, they cannot alleviate the impact of Streptococcus suis STSLS on the body

Method used

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  • Application of ellipticine hydrochloride in preparation of anti-streptococcus suis hemolysin drug
  • Application of ellipticine hydrochloride in preparation of anti-streptococcus suis hemolysin drug
  • Application of ellipticine hydrochloride in preparation of anti-streptococcus suis hemolysin drug

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Experimental program
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Effect test

Embodiment 1

[0031](1) In a 96-well plate, add 50 μL of 2% sheep red blood cells suspended in PBS to 50 μL of ellipticine hydrochloride (EH) serially diluted in PBS, and incubate at 37°C for 1 hour, where, The EH concentrations were 1, 2, 4, 8, 16, 32, 64, 128 μg / mL, and 2.5% TritonX-100 was used as a positive control. The plate was then centrifuged at 500 g for 5 minutes, and 50 μL of supernatant from each well of the assay plate was transferred to a fresh 96-well plate. Hemolysis was confirmed by visual observation and measurement of absorbance at 543 nm.

[0032]See the resultfigure 1 , Ellipticine hydrochloride itself does not cause hemolysis of red blood cells.

[0033](2) Culture the Streptococcus suis SC19 strain at 37°C for 12 hours, centrifuge at 4°C and 10000 rpm for 10 minutes, and collect the supernatant. Different volumes of culture supernatant were added to 2% defibrinated sheep blood phosphate buffer solution (PBS, pH 7.4) (total volume 1 mL), and incubated at 37°C for 30 minutes. Final...

Embodiment 2

[0041](1) During the docking process of SLY and EH, the molecular docking mode of SLY and EH was analyzed using AUTODOCK4.2. The crystal structure of SLY is derived from the Protein Database (PDB) http: / / www.rcsb.org / structure / 3HVN. The 2D and 3D structures of EH were drawn by ChemBioDraw Ultra 14.0 and ChemBio3D Ultra 14.0, respectively. Through computational simulation methods, the binding pockets of proteins and small molecules such asImage 6 A, Ellipticine hydrochloride binds to the Pose1 region of the hemolysin protein. In addition, such asImage 6 As shown in B, 11 amino acids including amino acids I87, D86, L110, N112, D111, T195, K190, N50, T191, S374, N82, etc. form a very good hydrophobic pocket cavity. The hydrophobic pockets and small molecule plane hydrophobic properties form a very Good hydrophobic interaction mode, and dominates the interaction, and the amino acid S84, L110 and small molecules form a good hydrogen bond interaction.

[0042](2) Using isothermal calorimetry...

Embodiment 3

[0046]The mice used in the following experiments were seven-week-old female BALB / c mice purchased from China Three Gorges University. Animal experiments conform to animal ethics, and all experiments are conducted under the guidance of the Animal Experiment Protection Supervision and Control Committee of Huazhong Agricultural University (HZAUMO-2019-011).

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Abstract

The invention discloses an application of ellipticine hydrochloride in the preparation of an anti-streptococcus suis hemolysin drug, and belongs to the field of microbial infectious diseases and medicines. The invention finds that ellipticine hydrochloride can neutralize the toxicity of streptococcus suis hemolysin and has a protective effect on mice infected by streptococcus suis. Ellipticine orpharmaceutically acceptable salt thereof can be used for preparing an anti-streptococcus suis hemolysin drug and a drug for preventing or treating streptococcus suis infection. The new medicinal valueof ellipticine hydrochloride is found, and a new prevention and treatment drug is provided for streptococcus suis infection; ellipticine hydrochloride can neutralize the main virulence factor hemolysin of streptococcus suis and reduce the damage of the poisoning shock-like syndrome to the body.

Description

Technical field[0001]The present invention relates to the field of microbial infectious diseases and medicine, in particular to the application of ellipticine hydrochloride in the preparation of anti-streptococcal hemolysin drugs.Background technique[0002]Streptococcus suis is one of the most important zoonotic pathogens, which seriously threatens human health and the development of the pig industry, causing significant economic losses worldwide. According to incomplete statistics, since the first case of Streptococcus suis infection in Denmark in 1968, more than 1,600 cases of human infection with Streptococcus suis have been reported. Streptococcus suis infection can cause a variety of diseases, including sepsis, meningitis, endocarditis, and arthritis. The highest mortality rate is toxic shock-like syndrome (STSLS) caused by Streptococcus suis. STSLS is characterized by bacterial burden, inflammatory cytokine storm, and multi-system organ failure, which ultimately leads to acute ...

Claims

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Application Information

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IPC IPC(8): A61K31/475A61P31/04
CPCA61K31/475A61P31/04
Inventor 谭臣鲁浩刘曼莉王晨晨鲁文嘉李晓丹王湘如陈焕春
Owner HUAZHONG AGRI UNIV
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