Decoding potential host protein targets against Flaviviridae using protein-protein interaction network

Area of Science:

• Virology
• Computational Biology
• Drug Discovery

Background:

• Flaviviridae viruses (Dengue, Zika, Hepatitis C) cause significant global health issues.
• Understanding virus-host interactions is crucial for identifying therapeutic targets.
• Tissue-specific interactions can reveal novel drug targets and repurposing opportunities.

Purpose of the Study:

• To construct a comprehensive virus-human interactome for Flaviviridae.
• To identify druggable host protein targets exploited by these viruses.
• To propose potential repurposable drugs for broad-spectrum antiviral therapy.

Main Methods:

• Multi-step computational approach integrating virus-host protein-protein interactions (PPIs) with tissue-specific gene expression.
• Drug-target prediction analysis.
• Protein-ligand docking and molecular dynamics (MD) simulations.

Main Results:

• Identified druggable proteins: CCNA2 (PBMC), EIF2S2, CDK7, CARS (liver).
• Proposed repurposable drugs: Tamoxifen, Sirolimus, Entrectinib, L-cysteine.
• Validated complex stability using docking and MD simulations.

Conclusions:

• Common druggable host targets exist across DENV, ZIKV, and HCV infections.
• Findings support the development of unified therapeutic strategies against Flaviviridae.
• This research provides a foundation for novel broad-spectrum antiviral drug development.