Discovery of Anti-Japanese Encephalitis Compounds: Based on Natural Compound Library, Bioinformatics, Network...

Area of Science:

• Pharmacology
• Bioinformatics
• Traditional Chinese Medicine

Background:

• Japanese Encephalitis (JE) poses a significant health risk with limited treatment options.
• Traditional Chinese Medicine (TCM) offers a rich source of potential therapeutic compounds.

Purpose of the Study:

• To develop an integrated approach for identifying anti-JE compounds from Chinese herbs.
• To screen and validate compounds with both antiviral and anti-inflammatory properties against JE.

Main Methods:

• Constructed a TCM compound library and screened for compounds with Blood-Brain Barrier (BBB) permeability.
• Utilized network pharmacology, including PPI network and enrichment analysis, to identify core targets.
• Performed molecular docking and in vitro validation in JEV-infected cell models.

Main Results:

• Identified seven key herbs and 16 compounds, with six showing good druggability and BBB permeability.
• Network pharmacology highlighted five core targets for anti-neuroinflammatory activity and JEV proteins for antiviral activity.
• Caryophyllene oxide, Qingdainone, and Isoliquiritigenin demonstrated dual antiviral and anti-inflammatory effects by modulating the PTGS2/NF-κB pathway and targeting JEV proteins.

Conclusions:

• An integrative strategy combining TCM, bioinformatics, and pharmacology successfully identified novel anti-JE agents.
• Caryophyllene oxide, Qingdainone, and Isoliquiritigenin exhibit a dual mechanism of action, targeting both viral replication and host inflammation.
• These findings provide a foundation for developing multi-target natural compounds for JE treatment.