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Application of 25-hydroxycholesterol in inhibiting flaviviruses

A hydroxycholesterol and flavivirus technology, which can be used in antiviral agents, resistance to vector-borne diseases, and medical preparations containing active ingredients, etc. Effect

Active Publication Date: 2017-08-11
SUZHOU INST OF SYST MEDICINE +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of ISGs other than IFITM1 and IFITM3 (interferon-induced transmembrane 1 and 3proteins, interferon-induced transmembrane proteins) that play a key role in innate immunity against Zika virus infection is still unclear
[0004] Cholesterol-25-Hydroxylase (Cholesterol-25-Hydroxylase) can catalyze the conversion of cholesterol into 25-hydroxycholesterol (25-Hydroxycholesterol, 25HC), which is an oxidized steroidal alcohol naturally occurring in the human body (Holmes et al., 2011 ; Janowski et al., 1999; Kandutsch et al., 1978), its application in the inhibition of flaviviruses has not been reported

Method used

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  • Application of 25-hydroxycholesterol in inhibiting flaviviruses
  • Application of 25-hydroxycholesterol in inhibiting flaviviruses
  • Application of 25-hydroxycholesterol in inhibiting flaviviruses

Examples

Experimental program
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Effect test

Embodiment 1

[0034] (1) 25HC can effectively inhibit the replication of Zika virus in vitro.

[0035] Vero cells were pretreated with different concentrations of 25HC for 36 hours, solvent ethanol (EtOH) was used as a negative control, and then the toxicity of 25HC to cells was detected by MTT assay. The result is as figure 1 Shown in A: 10 μ M 25HC has no toxicity to Vero cells ( figure 1 A).

[0036] In order to detect the inhibitory effect of 25HC on Zika virus, Vero cells were pretreated with different concentrations of 25HC for 12 hours, and then infected with Zika virus GZ01 strain (MOI 0.1). After 48 hours, the supernatant of the cells was taken for a plaque test, or the cell lysate was taken for RT-qPCR to detect the virus titer, and the solvent EtOH was used as a control. Specific steps are as follows:

[0037] (1) Plaque test: spread 2×10 5 BHK-21 cells were incubated overnight in a 12-well plate. The cells were then washed once with PBS and incubated with the cell supernat...

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Abstract

The invention relates to the field of chemical drugs, and discloses an application of 25-hydroxycholesterol in inhibiting flaviviruses. Specifically, the invention discloses an application of the 25HC (25-hydroxycholesterol) in preparing medicines for preventing and / or treating flavivirus infection, in inhibiting the flaviviruses and in preparing medicines for preventing and / or treating microcephaly caused by Zika virus infection. The invention also discloses a pharmaceutical composition, wherein the pharmaceutical composition consists of the 25HC, at least one adjuvant agent conductive to inhibition of the flaviviruses and at least one pharmaceutically acceptable vector. With the application of the 25HC, the flaviviruses can be inhibited, so that a protecting effect is taken on a host; and specifically, the 25HC can be used for inhibiting the flavivirus infection in human cell, mouse and rhesus monkey models, and can be used for preventing and / or treating the microcephaly caused by Zika viruses.

Description

technical field [0001] The invention relates to the field of chemical drugs, in particular to the use of 25-hydroxycholesterol in inhibiting flaviviruses. Background technique [0002] Zika Virus (ZIKV) spreads very quickly because it is transmitted by mosquitoes, asymptomatic carriers and sexually, posing a threat to people's health. Zika virus was first isolated in 1947 from an infected rhesus monkey in the Zika jungle of Uganda. The first human infection was reported in 1952 (Dick, 1952; Dick et al., 1952). Previously, people infected with Zika virus produced only mild symptoms such as joint pain, fatigue, rash and conjunctivitis. Zika virus emerged in Brazil in 2015 with an unexpected outbreak of congenital malformations such as microcephaly, Guillain-Barré syndrome, and meningitis (Araujo et al., 2016; Cao-Lormeau et al., 2016; Carteaux et al. , 2016; Musso and Gubler, 2016). These severe neurologic manifestations are currently thought to be caused by occasional mic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/575A61P31/12
CPCA61K31/575Y02A50/30
Inventor 程根宏秦成峰许执恒李春峰邓永强王硕黄星耀
Owner SUZHOU INST OF SYST MEDICINE
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