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Application of YM201636 and pharmaceutically acceptable salt thereof in preparation of drugs for resisting enterovirus infection

A technology of YM201636 and 1.YM20163 is applied in the application field of preparing anti-enterovirus infection drugs, which can solve the problems of limited number of infections, can only target a single, easy to produce drug resistance, etc., and achieve high-efficiency anti-enterovirus, The effect of wide application prospects

Active Publication Date: 2020-08-07
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, co-infection of coxsackie virus and new enterovirus or genome recombination between viruses often occurs in patients with hand, foot and mouth disease, which brings new troubles to the prevention and control of hand, foot and mouth disease. The number of vaccines used to prevent and control infections is limited
[0004] At present, anti-enterovirus drugs mainly focus on a single type of enterovirus strain, such as the use of aminothiazoles or quinoline carboxamides or aromatic esters to achieve anti-EV71[1-3], and its mechanism is aimed at The EV71 virus replicates itself, is prone to drug resistance, and can only target a single enterovirus

Method used

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  • Application of YM201636 and pharmaceutically acceptable salt thereof in preparation of drugs for resisting enterovirus infection
  • Application of YM201636 and pharmaceutically acceptable salt thereof in preparation of drugs for resisting enterovirus infection
  • Application of YM201636 and pharmaceutically acceptable salt thereof in preparation of drugs for resisting enterovirus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 1. Experimental materials:

[0040] 1.1 Cells and viruses:

[0041]Human embryonic rhabdomyosarcoma (RD) cells (resource number: 3142C0001000000321) were obtained from the China Center for Type Culture Collection (CCTCC) (Wuhan, China). Enterovirus 71 (EV71) strain (Xiangyang-Hubei-09) was derived from the brain tissue of an infant who died of EV71 infection in Xiangyang, Hubei Province, China, and was previously isolated and preserved by the State Key Laboratory of Virology, Wuhan University (GenBank: JN230523.1), virus stocks were amplified in RD cells. The small molecule compound YM201636 was purchased from MCE (MedChemExpress) in the United States.

[0042] 2. Experimental methods and results:

[0043] 2.1 Cytotoxicity detection of YM201636 on RD cells

[0044] (1) Divide RD cells according to 5×10 5 Cells / well were seeded in a 12-well cell culture plate in DMEM medium containing 10% FBS and supplemented with 1% penicillin and streptomycin. at 37°C, 5% CO 2 c...

Embodiment 2

[0087] Embodiment 2: YM201636 inhibits the detection of EV71 replication activity in mice

[0088] The application of YM201636 in the preparation of medicines for treating or preventing enterovirus infection, the steps are:

[0089] 1. Experimental materials:

[0090] 1.1 Animals and viruses:

[0091] C57BL / 6WT mice were purchased from Shanghai Experimental Animal Center, and the mice were housed in individually ventilated cages under specific pathogen-free (SPF) conditions. Enterovirus 71 (EV71) strain (Xiangyang-Hubei-09) was derived from the brain tissue of an infant who died of EV71 infection in Xiangyang, Hubei Province, China, and was previously isolated from the State Key Laboratory of Virology, Wuhan University (GenBank: JN230523. 1), Virus stocks are amplified in RD cells. The small molecule compound YM201636 was purchased from MCE (MedChemExpress) in the United States.

[0092] 2. Experimental methods and results:

[0093] 2.1 Detection of the effect of YM201636...

Embodiment 3

[0105] Embodiment 3: the active detection of YM201636 anti-CVB3, PV1

[0106] The application of YM201636 in the preparation of medicines for treating or preventing enterovirus infection, the steps are:

[0107] 1. Experimental materials:

[0108] 1.1 Cells and viruses:

[0109] Human embryonic rhabdomyosarcoma (RD) cells were obtained from the China Center for Type Culture Collection (CCTCC) (Wuhan, China). CVB3 (Nancy strain) (preservation number: GDV015) and PV1 (vaccine strain) (preservation number: GDV057) were derived from the China Center for Type Culture Collection (CCTCC) (Wuhan, China), and the virus stocks were amplified in RD cells. The small molecule compound YM201636 was purchased from MCE (MedChemExpress) in the United States.

[0110] 2. Experimental methods and results:

[0111] CVB3 and PV1 infect RD cells, and the viruses produce dsRNA during intracellular replication. Therefore, the immunofluorescence technique was used to evaluate the level of virus r...

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Abstract

The invention belongs to the technical field of biotechnology and biomedicine, and discloses an application of YM201636 and a pharmaceutically acceptable salt thereof in preparation of drugs for resisting enterovirus infection. The molecular formula of the YM20163 is C25H21N7O3. The method is based on the replication generality of enteroviruses in host cells, a small molecular compound YM201636 isadopted, a host cell PIKFYVE protein is specifically targeted so that the membrane components of the organelle are blocked, namely, the link from the early endosome to the late endosome is inhibited,normal formation of an endocytosis sorting transport complex (ESCRT) membrane transport complex is blocked, and an ESCRT complex mediated enterovirus replication complex is destroyed, so that the replication level of enteroviruses is inhibited, the purpose of controlling various enteroviruses is achieved, and a broad-spectrum and efficient enterovirus resisting effect is achieved.

Description

technical field [0001] The invention belongs to the technical fields of biotechnology and biomedicine, and particularly relates to the application of YM201636 and a pharmaceutically acceptable salt thereof in the preparation of anti-enterovirus infection drugs. Background technique [0002] Enterovirus infection is an infectious disease widely distributed around the world, which can occur in both adults and children, especially in children. The clinical manifestations are rashes, blisters, general fatigue, etc. in the extremities of mild patients; severe systemic damage to vital organs (including brain, heart and liver) occurs in severe patients, and the prognosis is poor, which can lead to sequelae or death. Enteroviruses include poliovirus (Poliovirus), Coxsackie virus (Coxsackie virus), enterocytopathic human orphan virus (Enterocytopathic human orphan virus, ECHO referred to as Echo virus) and new enteroviruses serotype. The virus infection of this genus is widely dist...

Claims

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Application Information

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IPC IPC(8): A61K31/5377A61P31/14
CPCA61K31/5377A61P31/14Y02A50/30
Inventor 罗震吴建国梁艺聪邬开朗苏芮
Owner JINAN UNIVERSITY
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