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25-Hydroxy cholesterol effectively inhibits Japanese encephalitis virus infection in a cellular model
Km Archana1, Bushra Qazi1, Babita Bohra1
1Division of Virus Research and Therapeutics, CSIR-Central Drug Research Institute, Lucknow, 226031, UP, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
Biochemical and Biophysical Research Communications
|August 15, 2025
Summary
25-hydroxycholesterol (25-HC) effectively prevents Japanese encephalitis virus (JEV) infection by inhibiting viral envelope protein expression. This finding suggests 25-HC as a potential broad-spectrum antiviral therapeutic against flaviviruses.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Japanese encephalitis virus (JEV) is a significant global health threat causing acute encephalitis.
- No FDA-approved treatments currently exist for JEV infections.
- 25-hydroxycholesterol (25-HC), an oxysterol, is upregulated during viral infections.
Purpose of the Study:
- To investigate the potential of 25-hydroxycholesterol (25-HC) as an antiviral agent against Japanese encephalitis virus (JEV).
- To determine the efficacy and safety of 25-HC in inhibiting JEV infection in cell culture.
Main Methods:
- Utilized Vero cells to assess the antiviral activity of 25-HC against JEV.
- Quantified JEV inhibition using IC50 and CC50 values.
- Measured JEV envelope (E) protein RNA levels and protein expression in the presence of 25-HC.
Main Results:
- 25-HC demonstrated significant inhibition of JEV infection in Vero cells with an IC50 of approximately 4.18 μM.
- 25-HC exhibited no cytotoxicity, with CC50 values greater than 50 μM.
- A dose-dependent reduction in JEV E protein RNA and protein levels was observed with 25-HC treatment.
Conclusions:
- 25-HC effectively inhibits JEV infection, likely by modulating host plasma membrane cholesterol levels and impairing viral entry and fusion.
- 25-HC shows promise as a potential broad-spectrum antiviral therapeutic for flaviviral infections, including JEV, Zika, and Dengue viruses.
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